Author: "Swertz, Morris" / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Swertz, Morris"' showing total 296 results

Start Over Author "Swertz, Morris" Database OAIster

296 results on '"Swertz, Morris"'

1. Metadata for Data dIscoverability aNd Study rEplicability in obseRVAtional Studies (MINERVA): Development and Pilot of a Metadata List and Catalogue in Europe

Author: Infection & Immunity, Child Health, Data Science & Biostatistiek, Pajouheshnia, Romin, Gini, Rosa, Gutierrez, Lia, Swertz, Morris A, Hyde, Eleanor, Sturkenboom, Miriam, Arana, Alejandro, Franzoni, Carla, Ehrenstein, Vera, Roberto, Giuseppe, Gil, Miguel, Maciá, Miguel Angel, Schäfer, Wiebke, Haug, Ulrike, Thurin, Nicolas H, Lassalle, Régis, Droz-Perroteau, Cécile, Zaccagnino, Silvia, Busto, Maria Paula, Middelkoop, Bas, Gembert, Karin, Sanchez-Saez, Francisco, Rodriguez-Bernal, Clara, Sanfélix-Gimeno, Gabriel, Hurtado, Isabel, Acosta, Manuel Barreiro de, Poblador-Plou, Beatriz, Carmona-Pírez, Jonás, Gimeno-Miguel, Antonio, Prados-Torres, Alexandra, Schultze, Anna, Jansen, Ella, Herings, Ron, Kuiper, Josine, Locatelli, Igor, Jazbar, Janja, Žerovnik, Špela, Kos, Mitja, Smit, Steven, Lind, Sirje, Metspalu, Andres, Simou, Stefania, Hedenmalm, Karin, Cochino, Ana, Alcini, Paolo, Kurz, Xavier, Perez-Gutthann, Susana, Infection & Immunity, Child Health, Data Science & Biostatistiek, Pajouheshnia, Romin, Gini, Rosa, Gutierrez, Lia, Swertz, Morris A, Hyde, Eleanor, Sturkenboom, Miriam, Arana, Alejandro, Franzoni, Carla, Ehrenstein, Vera, Roberto, Giuseppe, Gil, Miguel, Maciá, Miguel Angel, Schäfer, Wiebke, Haug, Ulrike, Thurin, Nicolas H, Lassalle, Régis, Droz-Perroteau, Cécile, Zaccagnino, Silvia, Busto, Maria Paula, Middelkoop, Bas, Gembert, Karin, Sanchez-Saez, Francisco, Rodriguez-Bernal, Clara, Sanfélix-Gimeno, Gabriel, Hurtado, Isabel, Acosta, Manuel Barreiro de, Poblador-Plou, Beatriz, Carmona-Pírez, Jonás, Gimeno-Miguel, Antonio, Prados-Torres, Alexandra, Schultze, Anna, Jansen, Ella, Herings, Ron, Kuiper, Josine, Locatelli, Igor, Jazbar, Janja, Žerovnik, Špela, Kos, Mitja, Smit, Steven, Lind, Sirje, Metspalu, Andres, Simou, Stefania, Hedenmalm, Karin, Cochino, Ana, Alcini, Paolo, Kurz, Xavier, and Perez-Gutthann, Susana
Published: 2024

2. Metadata for Data dIscoverability aNd Study rEplicability in obseRVAtional Studies (MINERVA): Lessons Learnt From the MINERVA Project in Europe

Author: Data Science & Biostatistiek, Child Health, Infection & Immunity, Gini, Rosa, Pajouheshnia, Romin, Gutierrez, Lia, Swertz, Morris A, Hyde, Eleanor, Sturkenboom, Miriam, Arana, Alejandro, Franzoni, Carla, Ehrenstein, Vera, Roberto, Giuseppe, Gil, Miguel, Maciá, Miguel Angel, Schäfer, Wiebke, Haug, Ulrike, Thurin, Nicolas H, Lassalle, Régis, Droz-Perroteau, Cécile, Zaccagnino, Silvia, Busto, Maria Paula, Middelkoop, Bas, Gembert, Karin, Sanchez-Saez, Francisco, Rodriguez-Bernal, Clara, Sanfélix-Gimeno, Gabriel, Hurtado, Isabel, Acosta, Manuel Barreiro de, Poblador-Plou, Beatriz, Carmona-Pírez, Jonás, Gimeno-Miguel, Antonio, Prados-Torres, Alexandra, Schultze, Anna, Jansen, Ella, Herings, Ron, Kuiper, Josine, Locatelli, Igor, Jazbar, Janja, Žerovnik, Špela, Kos, Mitja, Smit, Steven, Lind, Sirje, Metspalu, Andres, Simou, Stefania, Hedenmalm, Karin, Cochino, Ana, Alcini, Paolo, Kurz, Xavier, Perez-Gutthann, Susana, Data Science & Biostatistiek, Child Health, Infection & Immunity, Gini, Rosa, Pajouheshnia, Romin, Gutierrez, Lia, Swertz, Morris A, Hyde, Eleanor, Sturkenboom, Miriam, Arana, Alejandro, Franzoni, Carla, Ehrenstein, Vera, Roberto, Giuseppe, Gil, Miguel, Maciá, Miguel Angel, Schäfer, Wiebke, Haug, Ulrike, Thurin, Nicolas H, Lassalle, Régis, Droz-Perroteau, Cécile, Zaccagnino, Silvia, Busto, Maria Paula, Middelkoop, Bas, Gembert, Karin, Sanchez-Saez, Francisco, Rodriguez-Bernal, Clara, Sanfélix-Gimeno, Gabriel, Hurtado, Isabel, Acosta, Manuel Barreiro de, Poblador-Plou, Beatriz, Carmona-Pírez, Jonás, Gimeno-Miguel, Antonio, Prados-Torres, Alexandra, Schultze, Anna, Jansen, Ella, Herings, Ron, Kuiper, Josine, Locatelli, Igor, Jazbar, Janja, Žerovnik, Špela, Kos, Mitja, Smit, Steven, Lind, Sirje, Metspalu, Andres, Simou, Stefania, Hedenmalm, Karin, Cochino, Ana, Alcini, Paolo, Kurz, Xavier, and Perez-Gutthann, Susana
Published: 2024

3. Comparing Sequence-Based and Literature-Based Pathogenicity Scoring Methods for Human Variants

Author: Mottin, Luc, Naderi, Nona, Mottaz, Anaïs, Michel, Pierre André, Been, Gerieke, Johansson, Lennart, Swertz, Morris, Stubbs, Andrew, Pasche, Emilie, Gobeill, Julien, Ruch, Patrick, Mottin, Luc, Naderi, Nona, Mottaz, Anaïs, Michel, Pierre André, Been, Gerieke, Johansson, Lennart, Swertz, Morris, Stubbs, Andrew, Pasche, Emilie, Gobeill, Julien, and Ruch, Patrick
Abstract: Assessing the pathogenicity of genetic variants is a critical aspect of genomic medicine and precision healthcare. Over the last decades, the identification of genetic variants and their characterization has become simpler (advent of high-throughput sequencing technologies, analysis, and visualization support tools, etc.). However, the quality of assessments to distinguish benign from pathogenic variants is critical to inform clinical decision-making and improve patient outcomes. In this article, we investigate the relationships using correlation tests between the characterization of genetic variants in the literature and their pathogenicity scores computed by two state-of-the-art assessment tools (SIFT and PolyPhen-2).
Published: 2024

4. Urban environment in pregnancy and postpartum depression:An individual participant data meta-analysis of 12 European birth cohorts

Author: Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., Pedersen, Marie, Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., and Pedersen, Marie
Abstract: Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). Objectives: We investigated associations between urban environment exposures during pregnancy and PPD. Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686–30,716 depending on exposure; representing 26–46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3–18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. Discussion: The study findings suggest that
Published: 2024

5. Urban environment in pregnancy and postpartum depression:An individual participant data meta-analysis of 12 European birth cohorts

Author: Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., Pedersen, Marie, Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., and Pedersen, Marie
Abstract: Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). Objectives: We investigated associations between urban environment exposures during pregnancy and PPD. Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686–30,716 depending on exposure; representing 26–46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3–18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposur
Published: 2024

6. Urban environment in pregnancy and postpartum depression:An individual participant data meta-analysis of 12 European birth cohorts

Author: Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., Pedersen, Marie, Cadman, Tim, Strandberg-Larsen, Katrine, Calas, Lucinda, Christiansen, Malina, Culpin, Iryna, Dadvand, Payam, de Castro, Montserrat, Foraster, Maria, Fossati, Serena, Guxens, Mònica, Harris, Jennifer R., Hillegers, Manon, Jaddoe, Vincent, Lee, Yunsung, Lepeule, Johanna, el Marroun, Hanan, Maule, Milena, McEachen, Rosie, Moccia, Chiara, Nader, Johanna, Nieuwenhuijsen, Mark, Nybo Andersen, Anne Marie, Pearson, Rebecca, Swertz, Morris, Vafeiadi, Marina, Vrijheid, Martine, Wright, John, Lawlor, Deborah A., and Pedersen, Marie
Abstract: Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). Objectives: We investigated associations between urban environment exposures during pregnancy and PPD. Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686–30,716 depending on exposure; representing 26–46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3–18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. Discussion: The study findings suggest that
Published: 2024

7. A Resource for Guiding Data Stewards to Make European Rare Disease Patient Registries FAIR

Author: European Commission, van Damme, Philip [0000-0002-7124-8949], Alarcón-Moreno, Pablo [0000-0001-5974-589X], Bernabé, César Henrique [0000-0003-1795-5930], Cámara, Alberto [0000-0001-5613-9704], Dos Santos Vieira, Bruna [0000-0001-7893-0505], van der Velde, K. Joeri [0000-0002-0934-8375], Zhang, Shuxin [0000-0003-4715-9070], Carta, Claudio [0000-0003-3545-198X], Cornet, Ronald [0000-0002-1704-5980], t Hoen, Peter A.C.[0000-0003-4450-3112], Jacobsen, Annika [0000-0003-4818-2360], Swertz, Morris A. [0000-0002-0979-3401], Roos, Marco [0000-0002-8691-772X], Benis, Nirupama [0000-0002-2101-6154], van Damme, Philip, Alarcón-Moreno, Pablo, Bernabé, César Henrique, Cámara, Alberto, Le Cornec, Clémence M. A., Dos Santos Vieira, Bruna, Van der Velde, K. Joeri, Zhang, Shuxin, Carta, Claudio, Cornet, Ronald, t Hoen, Peter A.C., Jacobsen, Annika, Swertz, Morris A., Roos, Marco, Benis, Nirupama, European Commission, van Damme, Philip [0000-0002-7124-8949], Alarcón-Moreno, Pablo [0000-0001-5974-589X], Bernabé, César Henrique [0000-0003-1795-5930], Cámara, Alberto [0000-0001-5613-9704], Dos Santos Vieira, Bruna [0000-0001-7893-0505], van der Velde, K. Joeri [0000-0002-0934-8375], Zhang, Shuxin [0000-0003-4715-9070], Carta, Claudio [0000-0003-3545-198X], Cornet, Ronald [0000-0002-1704-5980], t Hoen, Peter A.C.[0000-0003-4450-3112], Jacobsen, Annika [0000-0003-4818-2360], Swertz, Morris A. [0000-0002-0979-3401], Roos, Marco [0000-0002-8691-772X], Benis, Nirupama [0000-0002-2101-6154], van Damme, Philip, Alarcón-Moreno, Pablo, Bernabé, César Henrique, Cámara, Alberto, Le Cornec, Clémence M. A., Dos Santos Vieira, Bruna, Van der Velde, K. Joeri, Zhang, Shuxin, Carta, Claudio, Cornet, Ronald, t Hoen, Peter A.C., Jacobsen, Annika, Swertz, Morris A., Roos, Marco, and Benis, Nirupama
Abstract: Objective: This paper reports on the development of a dynamic data management planning questionnaire to guide data stewards of the European Reference Network (ERN) rare disease patient registries to make their data findable, accessible, interoperable, and reusable (FAIR). As part of this work, the questionnaire was validated through expert review and aligned with existing resources on rare diseases and FAIR data management. Materials and Methods: The questionnaire was developed for the Data Stewardship Wizard, a tool for data management planning. Knowledge sources on FAIR data, ERN patient registries, and data management were used to compose questions. Ten domain experts validated the questionnaire. The topics in the questionnaire were aligned with existing knowledge bases. Results: A total of 57 questions were included in the questionnaire. Twenty-three references to the FAIR Cookbook and Research Data Management toolkit for Life Sciences were added. Expert validation provided a total of 166 comments on content, structure, and software-related issues. A public instance of the Data Stewardship Wizard was deployed for use by data stewards of ERN patient registries. Discussion: The questionnaire addresses issues that ERNs encounter when making their registries FAIR and follows the implementation choices made by the European rare disease community. A challenging task for future research is to extend the questionnaire to other types of registries and to validate with users. Conclusion: This smart questionnaire is the first model created for the Data Stewardship Wizard that helps ERN patient registries with making their data FAIR. It will assist data stewards in aligning their efforts and providing guidance on FAIR data.
Published: 2023

8. Surveyed common data access policies preferences amongst European Reference Networks

Author: European Commission, Cámara, Alberto [0000-0001-5613-9704], Benis, Nirupama [0000-0002-2101-6154], Vieira, Bruna Dos Santos [0000-0001-7893-0505], Ramírez Valiente, José Alberto [0000-0002-5951-2938], Van der Velde, K. Joeri [0000-0002-0934-8375], Zhang, Shuxin [0000-0003-4715-9070], Cornet, Ronald [0000-0002-1704-5980], Jacobsen, Annika [0000-0003-4818-2360], Roos, Marco [0000-0002-8691-772X], Swertz, Morris A. [0000-0002-0979-3401], Wilkinson, Mark D. [0000-0001-6960-357X], Cámara, Alberto, Benis, Nirupama, Bernabé, César Henrique, Coelho, Inés D., Le Cornec, Clémence M. A., Demir, Aylin, Vieira, Bruna Dos Santos, Ramírez Valiente, José Alberto, Van der Velde, K. Joeri, Zhang, Shuxin, Cornet, Ronald, Jacobsen, Annika, Roos, Marco, Schaefer, Franz, Swertz, Morris A., Wilkinson, Mark D., European Commission, Cámara, Alberto [0000-0001-5613-9704], Benis, Nirupama [0000-0002-2101-6154], Vieira, Bruna Dos Santos [0000-0001-7893-0505], Ramírez Valiente, José Alberto [0000-0002-5951-2938], Van der Velde, K. Joeri [0000-0002-0934-8375], Zhang, Shuxin [0000-0003-4715-9070], Cornet, Ronald [0000-0002-1704-5980], Jacobsen, Annika [0000-0003-4818-2360], Roos, Marco [0000-0002-8691-772X], Swertz, Morris A. [0000-0002-0979-3401], Wilkinson, Mark D. [0000-0001-6960-357X], Cámara, Alberto, Benis, Nirupama, Bernabé, César Henrique, Coelho, Inés D., Le Cornec, Clémence M. A., Demir, Aylin, Vieira, Bruna Dos Santos, Ramírez Valiente, José Alberto, Van der Velde, K. Joeri, Zhang, Shuxin, Cornet, Ronald, Jacobsen, Annika, Roos, Marco, Schaefer, Franz, Swertz, Morris A., and Wilkinson, Mark D.
Abstract: Background: Data sharing amongst existing Rare Disease (RD) registries, even though being a process that presents multiple barriers, would enrich and ease research, as well as facilitate interoperability between the registries themselves. Methods: To understand their preferences on sharing data, we surveyed 24 European Reference Networks (ERNs) from the RD Domain. Results: The answers show that most ERNs are willing to share a set of Common Data Elements for free with authenticated users at an aggregated or pseudonymized level the moment the data is collected. The one exception is the industry sector, to which ERNs prefer to ask for a fee. Objective: Our aim is to create a reference for how most RD registries are willing to share their data, improving the ability of other stakeholders to make informed decisions to make their data interoperable.
Published: 2023

9. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Author: Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppönen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kuehnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian'an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Mollegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter, de Mutsert, Renee, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefansson, Kari, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., Perry, John R. B., Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppönen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kuehnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian'an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Mollegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter, de Mutsert, Renee, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefansson, Kari, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., and Perry, John R. B.
Abstract: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.
Published: 2023
Full Text: View/download PDF

10. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, and Alembik, Yves
Abstract: Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.
Published: 2023

11. Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, May, Patrick, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, and May, Patrick
Abstract: Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.
Published: 2023

12. Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, May, Patrick, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, and May, Patrick
Abstract: Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.
Published: 2023

13. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, and Alembik, Yves
Abstract: Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.
Published: 2023

14. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, and Alembik, Yves
Abstract: Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.
Published: 2023

15. Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, May, Patrick, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Yaldiz, Burcu, Kucuk, Erdi, Hampstead, Juliet, Hofste, Tom, Pfundt, Rolph, Corominas Galbany, Jordi, Rinne, Tuula, Yntema, Helger G., Hoischen, Alexander, Nelen, Marcel, Gilissen, Christian, consortium, Solve-R. D., Riess, Olaf, Haack, Tobias B., Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoen, Peter A. C. T, Vissers, Lisenka E. L. M., Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, te Paske, Iris, Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Matalonga, Leslie, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Vandrovcova, Jana, Efthymiou, Stephanie, Morsy, Heba, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Abbott, Kristin M., Frederikse, Wilhemina Skerstjens, Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, de Sainte Agathe, Jean-Madeleine, Rooryck, Caroline, Lacombe, Didier, Trimouille, Aurelien, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Balicza, Peter, Molnar, Maria Judit, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Osorio, Andrés Nascimento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Beeson, David, Cossins, Judith, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Horvath, Rita, Chinnery, Patrick F., Ratnaike, Thiloka, Gao, Fei, Schon, Katherine, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Başak, Ayşe Nazlı, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Claeys, Kristl, Santen, Gijs W. E., Bijlsma, Emilia K., Hoffer, Mariette J. V., Ruivenkamp, Claudia A. L., Boztug, Kaan, Haimel, Matthias, Maystadt, Isabelle, Cordts, Isabelle, Deschauer, Marcus, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Depienne, Christel, Roos, Andreas, and May, Patrick
Abstract: Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.
Published: 2023

16. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, and Alembik, Yves
Abstract: Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.
Published: 2023

17. Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching

Author: Maassen, Willem, Legger, Geertje, Kul Cinar, Ovgu, van Daele, Paul, Gattorno, Marco, Bader-Meunier, Brigitte, Wouters, Carine, Briggs, Tracy, Johansson, Lennart, van der Velde, Joeri, Swertz, Morris, Omoyinmi, Ebun, Hoppenreijs, Esther, Belot, Alexandre, Eleftheriou, Despina, Caorsi, Roberta, Aeschlimann, Florence, Boursier, Guilaine, Brogan, Paul, Haimel, Matthias, van Gijn, Marielle, Maassen, Willem, Legger, Geertje, Kul Cinar, Ovgu, van Daele, Paul, Gattorno, Marco, Bader-Meunier, Brigitte, Wouters, Carine, Briggs, Tracy, Johansson, Lennart, van der Velde, Joeri, Swertz, Morris, Omoyinmi, Ebun, Hoppenreijs, Esther, Belot, Alexandre, Eleftheriou, Despina, Caorsi, Roberta, Aeschlimann, Florence, Boursier, Guilaine, Brogan, Paul, Haimel, Matthias, and van Gijn, Marielle
Abstract: Introduction: Accurate and standardized phenotypic descriptions are essential in diagnosing rare diseases and discovering new diseases, and the Human Phenotype Ontology (HPO) system was developed to provide a rich collection of hierarchical phenotypic descriptions. However, although the HPO terms for inborn errors of immunity have been improved and curated, it has not been investigated whether this curation improves the diagnosis of systemic autoinflammatory disease (SAID) patients. Here, we aimed to study if improved HPO annotation for SAIDs enhanced SAID identification and to demonstrate the potential of phenotype-driven genome diagnostics using curated HPO terms for SAIDs. Methods: We collected HPO terms from 98 genetically confirmed SAID patients across eight different European SAID expertise centers and used the LIRICAL (Likelihood Ratio Interpretation of Clinical Abnormalities) computational algorithm to estimate the effect of HPO curation on the prioritization of the correct SAID for each patient. Results: Our results show that the percentage of correct diagnoses increased from 66% to 86% and that the number of diagnoses with the highest ranking increased from 38 to 45. In a further pilot study, curation also improved HPO-based whole-exome sequencing (WES) analysis, diagnosing 10/12 patients before and 12/12 after curation. In addition, the average number of candidate diseases that needed to be interpreted decreased from 35 to 2. Discussion: This study demonstrates that curation of HPO terms can increase identification of the correct diagnosis, emphasizing the high potential of HPO-based genome diagnostics for SAIDs.
Published: 2023

18. Life course of retrospective harmonization initiatives:key elements to consider

Author: Fortier, Isabel, Wey, Tina W., Bergeron, Julie, Pinot de Moira, Angela, Nybo-Andersen, Anne-Marie, Bishop, Tom, Murtagh, Madeleine J., Miocevic, Milica, Swertz, Morris A., van Enckevort, Esther, Marcon, Yannick, Mayrhofer, Michaela. Th., Ornelas, Jos Pedro, Sebert, Sylvain, Santos, Ana Cristina, Rocha, Artur, Wilson, Rebecca C., Griffith, Lauren E., Burton, Paul, Fortier, Isabel, Wey, Tina W., Bergeron, Julie, Pinot de Moira, Angela, Nybo-Andersen, Anne-Marie, Bishop, Tom, Murtagh, Madeleine J., Miocevic, Milica, Swertz, Morris A., van Enckevort, Esther, Marcon, Yannick, Mayrhofer, Michaela. Th., Ornelas, Jos Pedro, Sebert, Sylvain, Santos, Ana Cristina, Rocha, Artur, Wilson, Rebecca C., Griffith, Lauren E., and Burton, Paul
Abstract: Optimizing research on the developmental origins of health and disease (DOHaD) involves implementing initiatives maximizing the use of the available cohort study data; achieving sufficient statistical power to support subgroup analysis; and using participant data presenting adequate follow-up and exposure heterogeneity. It also involves being able to undertake comparison, cross-validation, or replication across data sets. To answer these requirements, cohort study data need to be findable, accessible, interoperable, and reusable (FAIR), and more particularly, it often needs to be harmonized. Harmonization is required to achieve or improve comparability of the putatively equivalent measures collected by different studies on different individuals. Although the characteristics of the research initiatives generating and using harmonized data vary extensively, all are confronted by similar issues. Having to collate, understand, process, host, and co-analyze data from individual cohort studies is particularly challenging. The scientific success and timely management of projects can be facilitated by an ensemble of factors. The current document provides an overview of the 'life course' of research projects requiring harmonization of existing data and highlights key elements to be considered from the inception to the end of the project.
Published: 2023

19. Life course of retrospective harmonization initiatives:key elements to consider

Author: Fortier, Isabel, Wey, Tina W., Bergeron, Julie, Pinot de Moira, Angela, Nybo-Andersen, Anne-Marie, Bishop, Tom, Murtagh, Madeleine J., Miocevic, Milica, Swertz, Morris A., van Enckevort, Esther, Marcon, Yannick, Mayrhofer, Michaela. Th., Ornelas, Jos Pedro, Sebert, Sylvain, Santos, Ana Cristina, Rocha, Artur, Wilson, Rebecca C., Griffith, Lauren E., Burton, Paul, Fortier, Isabel, Wey, Tina W., Bergeron, Julie, Pinot de Moira, Angela, Nybo-Andersen, Anne-Marie, Bishop, Tom, Murtagh, Madeleine J., Miocevic, Milica, Swertz, Morris A., van Enckevort, Esther, Marcon, Yannick, Mayrhofer, Michaela. Th., Ornelas, Jos Pedro, Sebert, Sylvain, Santos, Ana Cristina, Rocha, Artur, Wilson, Rebecca C., Griffith, Lauren E., and Burton, Paul
Abstract: Optimizing research on the developmental origins of health and disease (DOHaD) involves implementing initiatives maximizing the use of the available cohort study data; achieving sufficient statistical power to support subgroup analysis; and using participant data presenting adequate follow-up and exposure heterogeneity. It also involves being able to undertake comparison, cross-validation, or replication across data sets. To answer these requirements, cohort study data need to be findable, accessible, interoperable, and reusable (FAIR), and more particularly, it often needs to be harmonized. Harmonization is required to achieve or improve comparability of the putatively equivalent measures collected by different studies on different individuals. Although the characteristics of the research initiatives generating and using harmonized data vary extensively, all are confronted by similar issues. Having to collate, understand, process, host, and co-analyze data from individual cohort studies is particularly challenging. The scientific success and timely management of projects can be facilitated by an ensemble of factors. The current document provides an overview of the 'life course' of research projects requiring harmonization of existing data and highlights key elements to be considered from the inception to the end of the project.
Published: 2023

20. Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers

Author: Lopera-Maya, Esteban A., Li, Shuang, de Brouwer, Remco, Nolte, Ilja M., van Breen, Justin, Bosman, Laurens P., Groeneweg, Judith A., de Groot, Natasja M.S., Jongbloed, Jan D.H., Swertz, Morris A., Snieder, Harold, Franke, Lude, Wijmenga, Cisca, de Boer, Rudolf A., Deelen, Patrick, van der Zwaag, Paul A., Sanna, Serena, Lopera-Maya, Esteban A., Li, Shuang, de Brouwer, Remco, Nolte, Ilja M., van Breen, Justin, Bosman, Laurens P., Groeneweg, Judith A., de Groot, Natasja M.S., Jongbloed, Jan D.H., Swertz, Morris A., Snieder, Harold, Franke, Lude, Wijmenga, Cisca, de Boer, Rudolf A., Deelen, Patrick, van der Zwaag, Paul A., and Sanna, Serena
Abstract: The c.40_42delAGA variant in the phospholamban gene (PLN) has been associated with dilated and arrhythmogenic cardiomyopathy, with up to 70% of carriers experiencing a major cardiac event by age 70. However, there are carriers who remain asymptomatic at older ages. To understand the mechanisms behind this incomplete penetrance, we evaluated potential phenotypic and genetic modifiers in 74 PLN:c.40_42delAGA carriers identified in 36,339 participants of the Lifelines population cohort. Asymptomatic carriers (N = 48) showed shorter QRS duration (− 5.73 ms, q value = 0.001) compared to asymptomatic non-carriers, an effect we could replicate in two different independent cohorts. Furthermore, symptomatic carriers showed a higher correlation (r Pearson = 0.17) between polygenic predisposition to higher QRS (PGSQRS) and QRS (p value = 1.98 × 10–8), suggesting that the effect of the genetic variation on cardiac rhythm might be increased in symptomatic carriers. Our results allow for improved clinical interpretation for asymptomatic carriers, while our approach could guide future studies on genetic diseases with incomplete penetrance. Graphical abstract: [Figure not available: see fulltext.].
Published: 2023

21. Environmental factors shaping the gut microbiome in a Dutch population

Author: Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., Weersma, Rinse K., Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., and Weersma, Rinse K.
Abstract: The gut microbiome is associated with diverse diseases1–3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.
Published: 2022

22. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Abstract: The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.
Published: 2022

23. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Abstract: In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project-Building an ecosystem for better monitoring and communicating safety of medicines use in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation-with the vision that there is a societal obligation to rapidly reduce uncertainty about the safety of medication use in pregnancy and breastfeeding. The present paper introduces the set of concepts used to describe the European data sources involved in the ConcePTION project and illustrates the ConcePTION Common Data Model (CDM), which serves as the keystone of the federated ConcePTION network. Based on data availability and content analysis of 21 European data sources, the ConcePTION CDM has been structured with six tables designed to capture data from routine healthcare, three tables for data from public health surveillance activities, three curated tables for derived data on population (e.g., observation time and mother-child linkage), plus four metadata tables. By its first anniversary, the ConcePTION CDM has enabled 13 data sources to run common scripts to contribute to major European projects, demonstrating its capacity to facilitate effective and transparent deployment of distributed analytics, and its potential to address questions about utilization, effectiveness, and safety of medicines in special populations, including during pregnancy and breastfeeding, and, more broadly, in the general population.
Published: 2022

24. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

25. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

26. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

27. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

28. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Author: Hop, Paul J., Zwamborn, Ramona A.J., Hannon, Eilis, Shireby, Gemma L., Nabais, Marta F., Walker, Emma M., van Rheenen, Wouter, van Vugt, Joke J.F.A., Dekker, Annelot M., Westeneng, Henk-Jan, Tazelaar, Gijs H.P., van Eijk, Kristel R., Moisse, Matthieu, Baird, Denis, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Ticozzi, Nicola, Ratti, Antonia, Cooper-Knock, Jonathan, Morrison, Karen E., Shaw, Pamela J., Basak, A. Nazli, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Canosa, Antonio, Brunetti, Maura, Grassano, Maurizio, Gotkine, Marc, Lerner, Yossef, Zabari, Michal, Vourc'H, Patrick, Corcia, Philippe, Couratier, Philippe, Mora Pardina, Jesus S., Salas, Teresa, Dion, Patrick, Ross, Jay P., Henderson, Robert D., Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Nicholson, Garth, Rowe, Dominic B., Pamphlett, Roger, Mather, Karen A., Sachdev, Perminder S., Furlong, Sarah, Garton, Fleur C., Henders, Anjali K., Lin, Tian, Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Williams, Kelly L., Neto, Miguel Mitne, Cauchi, Ruben J., Blair, Ian P., Kiernan, Matthew C., Drory, Vivian, Povedano, Monica, de Carvalho, Mamede, Pinto, Susana, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Landers, John E., Shaw, Christopher E., Andersen, Peter M., McRae, Allan F., van Es, Michael A., Pasterkamp, R. Jeroen, Wray, Naomi R., McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Al-Chalabi, Ammar, van den Berg, Leonard H., Van Damme, Philip, Mill, Jonathan, Veldink, Jan H., Heijmans, Bastiaan T., t Hoen, Peter A.C., van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Joukje J., van Greevenbroek, Marleen M.J., Stehouwer, Coen D.A., van der Kallen, Carla J.H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, Eka H.D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van 'T Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., Bensimon, Gilbert, Smith, George Davey, Hop, Paul J., Zwamborn, Ramona A.J., Hannon, Eilis, Shireby, Gemma L., Nabais, Marta F., Walker, Emma M., van Rheenen, Wouter, van Vugt, Joke J.F.A., Dekker, Annelot M., Westeneng, Henk-Jan, Tazelaar, Gijs H.P., van Eijk, Kristel R., Moisse, Matthieu, Baird, Denis, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Ticozzi, Nicola, Ratti, Antonia, Cooper-Knock, Jonathan, Morrison, Karen E., Shaw, Pamela J., Basak, A. Nazli, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Canosa, Antonio, Brunetti, Maura, Grassano, Maurizio, Gotkine, Marc, Lerner, Yossef, Zabari, Michal, Vourc'H, Patrick, Corcia, Philippe, Couratier, Philippe, Mora Pardina, Jesus S., Salas, Teresa, Dion, Patrick, Ross, Jay P., Henderson, Robert D., Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Nicholson, Garth, Rowe, Dominic B., Pamphlett, Roger, Mather, Karen A., Sachdev, Perminder S., Furlong, Sarah, Garton, Fleur C., Henders, Anjali K., Lin, Tian, Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Williams, Kelly L., Neto, Miguel Mitne, Cauchi, Ruben J., Blair, Ian P., Kiernan, Matthew C., Drory, Vivian, Povedano, Monica, de Carvalho, Mamede, Pinto, Susana, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Landers, John E., Shaw, Christopher E., Andersen, Peter M., McRae, Allan F., van Es, Michael A., Pasterkamp, R. Jeroen, Wray, Naomi R., McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Al-Chalabi, Ammar, van den Berg, Leonard H., Van Damme, Philip, Mill, Jonathan, Veldink, Jan H., Heijmans, Bastiaan T., t Hoen, Peter A.C., van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Joukje J., van Greevenbroek, Marleen M.J., Stehouwer, Coen D.A., van der Kallen, Carla J.H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, Eka H.D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van 'T Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., Bensimon, Gilbert, and Smith, George Davey
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Published: 2022
Full Text: View/download PDF

29. Environmental factors shaping the gut microbiome in a Dutch population

Author: IRAS OH Epidemiology Chemical Agents, Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., Weersma, Rinse K., IRAS OH Epidemiology Chemical Agents, Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., and Weersma, Rinse K.
Published: 2022

30. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

31. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

32. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

33. Environmental factors shaping the gut microbiome in a Dutch population

Author: IRAS OH Epidemiology Chemical Agents, Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., Weersma, Rinse K., IRAS OH Epidemiology Chemical Agents, Gacesa , Ranko, Kurilshikov, Alexander, Vich Vila, Arnau, Sinha, Trishla, Klaassen, M, Bolte, L.A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens-Konter, J.A.M., Lenters, Virissa, Björk, J.R., Swarte, J.C., Swertz, Morris A., Jansen, B.H.R., Gelderloos-Arends, J., Jankipersadsing, Soesma A, Hofker, M., Vermeulen, Roel, Sanna, S., Harmsen, H J M, Wijmenga, Cisca, Fu, J., Zhernakova, A., and Weersma, Rinse K.
Published: 2022

34. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

35. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

36. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

37. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, dIRAS RA-I&I RA, Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F, Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A, Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d'Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B, Jaddoe, Vincent W V, Kaakinen, Marika A, Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F, Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R, Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M, Vermeulen, Roel, Juola, Teija, and Sebert, Sylvain
Published: 2022

38. Semantic modelling of common data elements for rare disease registries, and a prototype workflow for their deployment over registry data

Author: Alarcón-Moreno, Pablo [0000-0001-5974-589X], Dos Santos Vieira, Bruna [0000-0002-7245-9588], Kaliyaperumal, Rajaram, Wilkinson, Mark D., Alarcón-Moreno, Pablo, Benis, Nirupama, Cornet, Ronald, Dos Santos Vieira, Bruna, Michel Dumontier, Michel, Bernabé, César Henrique, Jacobsen, Annika, Le Cornec, Clémence M. A., Prieto Godoy, Mario, Queralt-Rosinach, Núria, Schultze Kool, Leo J., Swertz, Morris A., van Damme, Philip, Van der Velde, K. Joeri, Lalout, Nawel, Zhang, Shuxin, Roos, Marco, Alarcón-Moreno, Pablo [0000-0001-5974-589X], Dos Santos Vieira, Bruna [0000-0002-7245-9588], Kaliyaperumal, Rajaram, Wilkinson, Mark D., Alarcón-Moreno, Pablo, Benis, Nirupama, Cornet, Ronald, Dos Santos Vieira, Bruna, Michel Dumontier, Michel, Bernabé, César Henrique, Jacobsen, Annika, Le Cornec, Clémence M. A., Prieto Godoy, Mario, Queralt-Rosinach, Núria, Schultze Kool, Leo J., Swertz, Morris A., van Damme, Philip, Van der Velde, K. Joeri, Lalout, Nawel, Zhang, Shuxin, and Roos, Marco
Abstract: Background The European Platform on Rare Disease Registration (EU RD Platform) aims to address the fragmentation of European rare disease (RD) patient data, scattered among hundreds of independent and non-coordinating registries, by establishing standards for integration and interoperability. The first practical output of this effort was a set of 16 Common Data Elements (CDEs) that should be implemented by all RD registries. Interoperability, however, requires decisions beyond data elements - including data models, formats, and semantics. Within the European Joint Programme on Rare Diseases (EJP RD), we aim to further the goals of the EU RD Platform by generating reusable RD semantic model templates that follow the FAIR Data Principles. Results Through a team-based iterative approach, we created semantically grounded models to represent each of the CDEs, using the SemanticScience Integrated Ontology as the core framework for representing the entities and their relationships. Within that framework, we mapped the concepts represented in the CDEs, and their possible values, into domain ontologies such as the Orphanet Rare Disease Ontology, Human Phenotype Ontology and National Cancer Institute Thesaurus. Finally, we created an exemplar, reusable ETL pipeline that we will be deploying over these non-coordinating data repositories to assist them in creating model-compliant FAIR data without requiring site-specific coding nor expertise in Linked Data or FAIR. Conclusions Within the EJP RD project, we determined that creating reusable, expert-designed templates reduced or eliminated the requirement for our participating biomedical domain experts and rare disease data hosts to understand OWL semantics. This enabled them to publish highly expressive FAIR data using tools and approaches that were already familiar to them.
Published: 2022

39. Towards an Interoperable Ecosystem of Research Cohort and Real-world Data Catalogues Enabling Multi-center Studies

Author: Swertz, Morris, van Enckevort, Esther, Oliveira, José Luis, Fortier, Isabel, Bergeron, Julie, Thurin, Nicolas H., Hyde, Eleanor, Kellmann, Alexander, Pahoueshnja, Romin, Sturkenboom, Miriam, Cunnington, Marianne, Nybo Andersen, Anne Marie, Marcon, Yannick, Gonçalves, Gonçalo, Gini, Rosa, Swertz, Morris, van Enckevort, Esther, Oliveira, José Luis, Fortier, Isabel, Bergeron, Julie, Thurin, Nicolas H., Hyde, Eleanor, Kellmann, Alexander, Pahoueshnja, Romin, Sturkenboom, Miriam, Cunnington, Marianne, Nybo Andersen, Anne Marie, Marcon, Yannick, Gonçalves, Gonçalo, and Gini, Rosa
Abstract: Objectives: Existing individual-level human data cover large populations on many dimensions such as lifestyle, demography, laboratory measures, clinical parameters, etc. Recent years have seen large investments in data catalogues to FAIRify data descriptions to capitalise on this great promise, i.e. make catalogue contents more Findable, Accessible, Interoperable and Reusable. However, their valuable diversity also created heterogeneity, which poses challenges to optimally exploit their richness. Methods: In this opinion review, we analyse catalogues for human subject research ranging from cohort studies to surveillance, administrative and healthcare records. Results: We observe that while these catalogues are heterogeneous, have various scopes, and use different terminologies, still the underlying concepts seem potentially harmonizable. We propose a unified framework to enable catalogue data sharing, with catalogues of multi-center cohorts nested as a special case in catalogues of real-world data sources. Moreover, we list recommendations to create an integrated community of metadata catalogues and an open catalogue ecosystem to sustain these efforts and maximise impact. Conclusions: We propose to embrace the autonomy of motivated catalogue teams and invest in their collaboration via minimal standardisation efforts such as clear data licensing, persistent identifiers for linking same records between catalogues, minimal metadata ‘common data elements’ using shared ontologies, symmetric architectures for data sharing (push/pull) with clear provenance tracks to process updates and acknowledge original contributors. And most importantly, we encourage the creation of environments for collaboration and resource sharing between catalogue developers, building on international networks such as OpenAIRE and research data alliance, as well as domain specific ESFRIs such as BBMRI and ELIXIR., OBJECTIVES: Existing individual-level human data cover large populations on many dimensions such as lifestyle, demography, laboratory measures, clinical parameters, etc. Recent years have seen large investments in data catalogues to FAIRify data descriptions to capitalise on this great promise, i.e. make catalogue contents more Findable, Accessible, Interoperable and Reusable. However, their valuable diversity also created heterogeneity, which poses challenges to optimally exploit their richness. METHODS: In this opinion review, we analyse catalogues for human subject research ranging from cohort studies to surveillance, administrative and healthcare records. RESULTS: We observe that while these catalogues are heterogeneous, have various scopes, and use different terminologies, still the underlying concepts seem potentially harmonizable. We propose a unified framework to enable catalogue data sharing, with catalogues of multi-center cohorts nested as a special case in catalogues of real-world data sources. Moreover, we list recommendations to create an integrated community of metadata catalogues and an open catalogue ecosystem to sustain these efforts and maximise impact. CONCLUSIONS: We propose to embrace the autonomy of motivated catalogue teams and invest in their collaboration via minimal standardisation efforts such as clear data licensing, persistent identifiers for linking same records between catalogues, minimal metadata 'common data elements' using shared ontologies, symmetric architectures for data sharing (push/pull) with clear provenance tracks to process updates and acknowledge original contributors. And most importantly, we encourage the creation of environments for collaboration and resource sharing between catalogue developers, building on international networks such as OpenAIRE and research data alliance, as well as domain specific ESFRIs such as BBMRI and ELIXIR.
Published: 2022

40. Towards FAIRification of sensitive and fragmented rare disease patient data: challenges and solutions in European reference network registries

Author: European Commission, Dos Santos Vieira, Bruna [0000-0002-7245-9588], Cámara, Alberto [0000-0001-5613-9704], Cornet, Ronald [0000-0002-1704-5980], Dos Santos Vieira, Bruna, Bernabé, César Henrique, Zhang, Shuxin, Abaza, H., Benis, Nirupama, Cámara, Alberto, Cornet, Ronald, Le Cornec, Clémence M. A., Hoen, Peter A. C., Schaefer, Franz, Van der Velde, K. Joeri, Swertz, Morris A., Wilkinson, Mark D., Jacobsen, Annika, Roos, Marco, European Commission, Dos Santos Vieira, Bruna [0000-0002-7245-9588], Cámara, Alberto [0000-0001-5613-9704], Cornet, Ronald [0000-0002-1704-5980], Dos Santos Vieira, Bruna, Bernabé, César Henrique, Zhang, Shuxin, Abaza, H., Benis, Nirupama, Cámara, Alberto, Cornet, Ronald, Le Cornec, Clémence M. A., Hoen, Peter A. C., Schaefer, Franz, Van der Velde, K. Joeri, Swertz, Morris A., Wilkinson, Mark D., Jacobsen, Annika, and Roos, Marco
Abstract: Introduction: Rare disease patient data are typically sensitive, present in multiple registries controlled by different custodians, and non-interoperable. Making these data Findable, Accessible, Interoperable, and Reusable (FAIR) for humans and machines at source enables federated discovery and analysis across data custodians. This facilitates accurate diagnosis, optimal clinical management, and personalised treatments. In Europe, twenty-four European Reference Networks (ERNs) work on rare disease registries in different clinical domains. The process and the implementation choices for making data FAIR (‘FAIRification’) differ among ERN registries. For example, registries use different software systems and are subject to different legal regulations. To support the ERNs in making informed decisions and to harmonise FAIRification, the FAIRification steward team was established to work as liaisons between ERNs and researchers from the European Joint Programme on Rare Diseases. Results: The FAIRification steward team inventoried the FAIRification challenges of the ERN registries and proposed solutions collectively with involved stakeholders to address them. Ninety-eight FAIRification challenges from 24 ERNs’ registries were collected and categorised into “training” (31), “community” (9), “modelling” (12), “implementation” (26), and “legal” (20). After curating and aggregating highly similar challenges, 41 unique FAIRification challenges remained. The two categories with the most challenges were “training” (15) and “implementation” (9), followed by “community” (7), and then “modelling” (5) and “legal” (5). To address all challenges, eleven types of solutions were proposed. Among them, the provision of guidelines and the organisation of training activities resolved the “training” challenges, which ranged from less-technical “coffee-rounds” to technical workshops, from informal FAIR Games to formal hackathons. Obtaining implementation support from technical experts was the
Published: 2022

41. Towards an Interoperable Ecosystem of Research Cohort and Real-world Data Catalogues Enabling Multi-center Studies

Author: Swertz, Morris, van Enckevort, Esther, Oliveira, José Luis, Fortier, Isabel, Bergeron, Julie, Thurin, Nicolas H., Hyde, Eleanor, Kellmann, Alexander, Pahoueshnja, Romin, Sturkenboom, Miriam, Cunnington, Marianne, Nybo Andersen, Anne Marie, Marcon, Yannick, Gonçalves, Gonçalo, Gini, Rosa, Swertz, Morris, van Enckevort, Esther, Oliveira, José Luis, Fortier, Isabel, Bergeron, Julie, Thurin, Nicolas H., Hyde, Eleanor, Kellmann, Alexander, Pahoueshnja, Romin, Sturkenboom, Miriam, Cunnington, Marianne, Nybo Andersen, Anne Marie, Marcon, Yannick, Gonçalves, Gonçalo, and Gini, Rosa
Abstract: Objectives: Existing individual-level human data cover large populations on many dimensions such as lifestyle, demography, laboratory measures, clinical parameters, etc. Recent years have seen large investments in data catalogues to FAIRify data descriptions to capitalise on this great promise, i.e. make catalogue contents more Findable, Accessible, Interoperable and Reusable. However, their valuable diversity also created heterogeneity, which poses challenges to optimally exploit their richness. Methods: In this opinion review, we analyse catalogues for human subject research ranging from cohort studies to surveillance, administrative and healthcare records. Results: We observe that while these catalogues are heterogeneous, have various scopes, and use different terminologies, still the underlying concepts seem potentially harmonizable. We propose a unified framework to enable catalogue data sharing, with catalogues of multi-center cohorts nested as a special case in catalogues of real-world data sources. Moreover, we list recommendations to create an integrated community of metadata catalogues and an open catalogue ecosystem to sustain these efforts and maximise impact. Conclusions: We propose to embrace the autonomy of motivated catalogue teams and invest in their collaboration via minimal standardisation efforts such as clear data licensing, persistent identifiers for linking same records between catalogues, minimal metadata ‘common data elements’ using shared ontologies, symmetric architectures for data sharing (push/pull) with clear provenance tracks to process updates and acknowledge original contributors. And most importantly, we encourage the creation of environments for collaboration and resource sharing between catalogue developers, building on international networks such as OpenAIRE and research data alliance, as well as domain specific ESFRIs such as BBMRI and ELIXIR., OBJECTIVES: Existing individual-level human data cover large populations on many dimensions such as lifestyle, demography, laboratory measures, clinical parameters, etc. Recent years have seen large investments in data catalogues to FAIRify data descriptions to capitalise on this great promise, i.e. make catalogue contents more Findable, Accessible, Interoperable and Reusable. However, their valuable diversity also created heterogeneity, which poses challenges to optimally exploit their richness. METHODS: In this opinion review, we analyse catalogues for human subject research ranging from cohort studies to surveillance, administrative and healthcare records. RESULTS: We observe that while these catalogues are heterogeneous, have various scopes, and use different terminologies, still the underlying concepts seem potentially harmonizable. We propose a unified framework to enable catalogue data sharing, with catalogues of multi-center cohorts nested as a special case in catalogues of real-world data sources. Moreover, we list recommendations to create an integrated community of metadata catalogues and an open catalogue ecosystem to sustain these efforts and maximise impact. CONCLUSIONS: We propose to embrace the autonomy of motivated catalogue teams and invest in their collaboration via minimal standardisation efforts such as clear data licensing, persistent identifiers for linking same records between catalogues, minimal metadata 'common data elements' using shared ontologies, symmetric architectures for data sharing (push/pull) with clear provenance tracks to process updates and acknowledge original contributors. And most importantly, we encourage the creation of environments for collaboration and resource sharing between catalogue developers, building on international networks such as OpenAIRE and research data alliance, as well as domain specific ESFRIs such as BBMRI and ELIXIR.
Published: 2022

42. Associations of early-life pet ownership with asthma and allergic sensitization:a meta-analysis of >77,000 children from the EU Child Cohort Network

Author: Moira, Angela Pinot de, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, Guillain, Blandine de Lauzon, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae-Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Meel, Evelien R. Van, Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, Andersen, Anne-Marie Nybo, Moira, Angela Pinot de, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, Guillain, Blandine de Lauzon, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae-Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Meel, Evelien R. Van, Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, and Andersen, Anne-Marie Nybo
Published: 2022

43. Associations of early-life pet ownership with asthma and allergic sensitization:A meta-analysis of more than 77,000 children from the EU Child Cohort Network

Author: Pinot de Moira, Angela, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, de Lauzon Guillain, Blandine, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Van Meel, Evelien R., Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, Nybo Andersen, Anne Marie, Pinot de Moira, Angela, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, de Lauzon Guillain, Blandine, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Van Meel, Evelien R., Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, and Nybo Andersen, Anne Marie
Abstract: Background: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. Objective: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. Methods: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. Results: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. Conclusion: Our findings do not support early-life cat and dog ownership in
Published: 2022

44. FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research

Author: van der Velde, K. Joeri, Singh, Gurnoor, Kaliyaperumal, Rajaram, Liao, Xiao Feng, de Ridder, Sander, Rebers, Susanne, Kerstens, Hindrik H.D., de Andrade, Fernanda, van Reeuwijk, Jeroen, De Gruyter, Fini E., Hiltemann, Saskia, Ligtvoet, Maarten, Weiss, Marjan M., van Deutekom, Hanneke W.M., Jansen, Anne M.L., Stubbs, Andrew P., Vissers, Lisenka E.L.M., Laros, Jeroen F.J., van Enckevort, Esther, Stemkens, Daphne, ‘t Hoen, Peter A.C., Beliën, Jeroen A.M., van Gijn, Mariëlle E., Swertz, Morris A., van der Velde, K. Joeri, Singh, Gurnoor, Kaliyaperumal, Rajaram, Liao, Xiao Feng, de Ridder, Sander, Rebers, Susanne, Kerstens, Hindrik H.D., de Andrade, Fernanda, van Reeuwijk, Jeroen, De Gruyter, Fini E., Hiltemann, Saskia, Ligtvoet, Maarten, Weiss, Marjan M., van Deutekom, Hanneke W.M., Jansen, Anne M.L., Stubbs, Andrew P., Vissers, Lisenka E.L.M., Laros, Jeroen F.J., van Enckevort, Esther, Stemkens, Daphne, ‘t Hoen, Peter A.C., Beliën, Jeroen A.M., van Gijn, Mariëlle E., and Swertz, Morris A.
Abstract: The genomes of thousands of individuals are profiled within Dutch healthcare and research each year. However, this valuable genomic data, associated clinical data and consent are captured in different ways and stored across many systems and organizations. This makes it difficult to discover rare disease patients, reuse data for personalized medicine and establish research cohorts based on specific parameters. FAIR Genomes aims to enable NGS data reuse by developing metadata standards for the data descriptions needed to FAIRify genomic data while also addressing ELSI issues. We developed a semantic schema of essential data elements harmonized with international FAIR initiatives. The FAIR Genomes schema v1.1 contains 110 elements in 9 modules. It reuses common ontologies such as NCIT, DUO and EDAM, only introducing new terms when necessary. The schema is represented by a YAML file that can be transformed into templates for data entry software (EDC) and programmatic interfaces (JSON, RDF) to ease genomic data sharing in research and healthcare. The schema, documentation and MOLGENIS reference implementation are available at https://fairgenomes.org.
Published: 2022

45. Associations of early-life pet ownership with asthma and allergic sensitization:a meta-analysis of >77,000 children from the EU Child Cohort Network

Author: Moira, Angela Pinot de, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, Guillain, Blandine de Lauzon, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae-Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Meel, Evelien R. Van, Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, Andersen, Anne-Marie Nybo, Moira, Angela Pinot de, Strandberg-Larsen, Katrine, Bishop, Tom, Pedersen, Marie, Avraam, Demetris, Cadman, Tim, Calas, Lucinda, Casas, Maribel, Guillain, Blandine de Lauzon, Elhakeem, Ahmed, Esplugues, Ana, Estarlich, Marisa, Foong, Rachel E., Haakma, Sido, Harris, Jennifer R., Huang, Rae-Chi, Inskip, Hazel, Lertxundi, Aitana, Mensink-Bout, Sara M., Nader, Johanna L.T., Pizzi, Costanza, Popovic, Maja, Salika, Theodosia, Sunyer, Jordi, Meel, Evelien R. Van, Swertz, Morris A., Jaddoe, Vincent W.V., Burton, Paul, Duijts, Liesbeth, and Andersen, Anne-Marie Nybo
Published: 2022

46. FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research

Author: Genetica Medische Informatica, Pathologie Moleculair, Infection & Immunity, van der Velde, K Joeri, Singh, Gurnoor, Kaliyaperumal, Rajaram, Liao, XiaoFeng, de Ridder, Sander, Rebers, Susanne, Kerstens, Hindrik H D, de Andrade, Fernanda, van Reeuwijk, Jeroen, De Gruyter, Fini E, Hiltemann, Saskia, Ligtvoet, Maarten, Weiss, Marjan M, van Deutekom, Hanneke W M, Jansen, Anne M L, Stubbs, Andrew P, Vissers, Lisenka E L M, Laros, Jeroen F J, van Enckevort, Esther, Stemkens, Daphne, 't Hoen, Peter A C, Beliën, Jeroen A M, van Gijn, Mariëlle E, Swertz, Morris A, Genetica Medische Informatica, Pathologie Moleculair, Infection & Immunity, van der Velde, K Joeri, Singh, Gurnoor, Kaliyaperumal, Rajaram, Liao, XiaoFeng, de Ridder, Sander, Rebers, Susanne, Kerstens, Hindrik H D, de Andrade, Fernanda, van Reeuwijk, Jeroen, De Gruyter, Fini E, Hiltemann, Saskia, Ligtvoet, Maarten, Weiss, Marjan M, van Deutekom, Hanneke W M, Jansen, Anne M L, Stubbs, Andrew P, Vissers, Lisenka E L M, Laros, Jeroen F J, van Enckevort, Esther, Stemkens, Daphne, 't Hoen, Peter A C, Beliën, Jeroen A M, van Gijn, Mariëlle E, and Swertz, Morris A
Published: 2022

47. From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

Author: Data Science & Biostatistiek, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, Gini, Rosa, Data Science & Biostatistiek, Thurin, Nicolas H, Pajouheshnia, Romin, Roberto, Giuseppe, Dodd, Caitlin, Hyeraci, Giulia, Bartolini, Claudia, Paoletti, Olga, Nordeng, Hedvig, Wallach-Kildemoes, Helle, Ehrenstein, Vera, Dudukina, Elena, MacDonald, Thomas, De Paoli, Giorgia, Loane, Maria, Damase-Michel, Christine, Beau, Anna-Belle, Droz-Perroteau, Cécile, Lassalle, Régis, Bergman, Jorieke, Swart, Karin, Schink, Tania, Cavero-Carbonell, Clara, Barrachina-Bonet, Laia, Gomez-Lumbreras, Ainhoa, Giner-Soriano, Maria, Aragón, María, Neville, Amanda J, Puccini, Aurora, Pierini, Anna, Ientile, Valentina, Trifirò, Gianluca, Rissmann, Anke, Leinonen, Maarit K, Martikainen, Visa, Jordan, Sue, Thayer, Daniel, Scanlon, Ieuan, Georgiou, Mary E, Cunnington, Marianne, Swertz, Morris, Sturkenboom, Miriam, and Gini, Rosa
Published: 2022

48. The Data Use Ontology to streamline responsible access to human biomedical datasets

Author: Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., Courtot, Mélanie, Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., and Courtot, Mélanie
Published: 2021

49. The Data Use Ontology to streamline responsible access to human biomedical datasets

Author: Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., Courtot, Mélanie, Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., and Courtot, Mélanie
Published: 2021

50. The Data Use Ontology to streamline responsible access to human biomedical datasets

Author: Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., Courtot, Mélanie, Lawson, Jonathan, Cabili, Moran N., Kerry, Giselle, Boughtwood, Tiffany, Thorogood, Adrian, Alper, Pinar, Bowers, Sarion R., Boyles, Rebecca R., Brookes, Anthony J., Brush, Matthew, Burdett, Tony, Clissold, Hayley, Donnelly, Stacey, Dyke, Stephanie O. M., Freeberg, Mallory A., Haendel, Melissa A., Hata, Chihiro, Holub, Petr, Jeanson, Francis, Jene, Aina, Kawashima, Minae, Kawashima, Shuichi, Konopko, Melissa, Kyomugisha, Irene, Li, Haoyuan, Linden, Mikael, Rodriguez, Laura Lyman, Morita, Mizuki, Mulder, Nicola, Muller, Jean, Nagaie, Satoshi, Nasir, Jamal, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura D., Pandya, Ravi N., Parkinson, Helen, Philippakis, Anthony A., Prasser, Fabian, Rambla, Jordi, Reinold, Kathy, Rushton, Gregory A., Saltzman, Andrea, Saunders, Gary, Sofia, Heidi J., Spalding, John D., Swertz, Morris A., Tulchinsky, Ilia, van Enckevort, Esther J., Varma, Susheel, Voisin, Craig, Yamamoto, Natsuko, Yamasaki, Chisato, Zass, Lyndon, Guidry Auvil, Jaime M., Nyrönen, Tommi H., and Courtot, Mélanie
Published: 2021

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Journal

Database

Publisher

296 results on '"Swertz, Morris"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources