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34 results on '"Salerno, William J."'

1. Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank

Author

Gaynor, Sheila M., Joseph, Tyler, Bai, Xiaodong, Zou, Yuxin, Boutkov, Boris, Maxwell, Evan K., Delaneau, Olivier, Hofmeister, Robin J., Krasheninina, Olga, Balasubramanian, Suganthi, Marcketta, Anthony, Backman, Joshua, Reid, Jeffrey G., Overton, John D., Lotta, Luca A., Marchini, Jonathan, Salerno, William J., Baras, Aris, Abecasis, Goncalo R., and Thornton, Timothy A.

Published
2024
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2. Genetic risk factors for COVID-19 and influenza are largely distinct

Author

Kosmicki, Jack A., Marcketta, Anthony, Sharma, Deepika, Di Gioia, Silvio Alessandro, Batista, Samantha, Yang, Xiao-Man, Tzoneva, Gannie, Martinez, Hector, Sidore, Carlo, Kessler, Michael D., Horowitz, Julie E., Roberts, Genevieve H. L., Justice, Anne E., Banerjee, Nilanjana, Coignet, Marie V., Leader, Joseph B., Park, Danny S., Lanche, Rouel, Maxwell, Evan, Knight, Spencer C., Bai, Xiaodong, Guturu, Harendra, Baltzell, Asher, Girshick, Ahna R., McCurdy, Shannon R., Partha, Raghavendran, Mansfield, Adam J., Turissini, David A., Zhang, Miao, Mbatchou, Joelle, Watanabe, Kyoko, Verma, Anurag, Sirugo, Giorgio, Ritchie, Marylyn D., Salerno, William J., Shuldiner, Alan R., Rader, Daniel J., Mirshahi, Tooraj, Marchini, Jonathan, Overton, John D., Carey, David J., Habegger, Lukas, Reid, Jeffrey G., Economides, Aris, Kyratsous, Christos, Karalis, Katia, Baum, Alina, Cantor, Michael N., Rand, Kristin A., Hong, Eurie L., Ball, Catherine A., Siminovitch, Katherine, Baras, Aris, Abecasis, Goncalo R., and Ferreira, Manuel A. R.

Published
2024
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3. Mapping and characterization of structural variation in 17,795 human genomes

Author

Abel, Haley J, Larson, David E, Regier, Allison A, Chiang, Colby, Das, Indraniel, Kanchi, Krishna L, Layer, Ryan M, Neale, Benjamin M, Salerno, William J, Reeves, Catherine, Buyske, Steven, Matise, Tara C, Muzny, Donna M, Zody, Michael C, Lander, Eric S, Dutcher, Susan K, Stitziel, Nathan O, and Hall, Ira M

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Generic health relevance, Alleles, Case-Control Studies, Epigenesis, Genetic, Female, Gene Dosage, Genetic Variation, Genetics, Population, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Male, Molecular Sequence Annotation, Quantitative Trait Loci, Racial Groups, Software, Whole Genome Sequencing, NHGRI Centers for Common Disease Genomics, General Science & Technology
Abstract

A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline1 to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0-11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing.

Published
2020

4. Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease

Author

Horowitz, Julie E., Kosmicki, Jack A., Damask, Amy, Sharma, Deepika, Roberts, Genevieve H. L., Justice, Anne E., Banerjee, Nilanjana, Coignet, Marie V., Yadav, Ashish, Leader, Joseph B., Marcketta, Anthony, Park, Danny S., Lanche, Rouel, Maxwell, Evan, Knight, Spencer C., Bai, Xiaodong, Guturu, Harendra, Sun, Dylan, Baltzell, Asher, Kury, Fabricio S. P., Backman, Joshua D., Girshick, Ahna R., O’Dushlaine, Colm, McCurdy, Shannon R., Partha, Raghavendran, Mansfield, Adam J., Turissini, David A., Li, Alexander H., Zhang, Miao, Mbatchou, Joelle, Watanabe, Kyoko, Gurski, Lauren, McCarthy, Shane E., Kang, Hyun M., Dobbyn, Lee, Stahl, Eli, Verma, Anurag, Sirugo, Giorgio, Ritchie, Marylyn D., Jones, Marcus, Balasubramanian, Suganthi, Siminovitch, Katherine, Salerno, William J., Shuldiner, Alan R., Rader, Daniel J., Mirshahi, Tooraj, Locke, Adam E., Marchini, Jonathan, Overton, John D., Carey, David J., Habegger, Lukas, Cantor, Michael N., Rand, Kristin A., Hong, Eurie L., Reid, Jeffrey G., Ball, Catherine A., Baras, Aris, Abecasis, Gonçalo R., and Ferreira, Manuel A. R.

Published
2022
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5. Exome sequencing and analysis of 454,787 UK Biobank participants

Author

Backman, Joshua D., Li, Alexander H., Marcketta, Anthony, Sun, Dylan, Mbatchou, Joelle, Kessler, Michael D., Benner, Christian, Liu, Daren, Locke, Adam E., Balasubramanian, Suganthi, Yadav, Ashish, Banerjee, Nilanjana, Gillies, Christopher E., Damask, Amy, Liu, Simon, Bai, Xiaodong, Hawes, Alicia, Maxwell, Evan, Gurski, Lauren, Watanabe, Kyoko, Kosmicki, Jack A., Rajagopal, Veera, Mighty, Jason, Jones, Marcus, Mitnaul, Lyndon, Stahl, Eli, Coppola, Giovanni, Jorgenson, Eric, Habegger, Lukas, Salerno, William J., Shuldiner, Alan R., Lotta, Luca A., Overton, John D., Cantor, Michael N., Reid, Jeffrey G., Yancopoulos, George, Kang, Hyun M., Marchini, Jonathan, Baras, Aris, Abecasis, Gonçalo R., and Ferreira, Manuel A. R.

Published
2021
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6. Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank

Author

Szustakowski, Joseph D., Balasubramanian, Suganthi, Kvikstad, Erika, Khalid, Shareef, Bronson, Paola G., Sasson, Ariella, Wong, Emily, Liu, Daren, Wade Davis, J., Haefliger, Carolina, Katrina Loomis, A., Mikkilineni, Rajesh, Noh, Hyun Ji, Wadhawan, Samir, Bai, Xiaodong, Hawes, Alicia, Krasheninina, Olga, Ulloa, Ricardo, Lopez, Alex E., Smith, Erin N., Waring, Jeffrey F., Whelan, Christopher D., Tsai, Ellen A., Overton, John D., Salerno, William J., Jacob, Howard, Szalma, Sandor, Runz, Heiko, Hinkle, Gregory, Nioi, Paul, Petrovski, Slavé, Miller, Melissa R., Baras, Aris, Mitnaul, Lyndon J., and Reid, Jeffrey G.

Published
2021
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7. Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

Author

Naj, Adam C., Lin, Honghuang, Vardarajan, Badri N., White, Simon, Lancour, Daniel, Ma, Yiyi, Schmidt, Michael, Sun, Fangui, Butkiewicz, Mariusz, Bush, William S., Kunkle, Brian W., Malamon, John, Amin, Najaf, Choi, Seung Hoan, Hamilton-Nelson, Kara L., van der Lee, Sven J., Gupta, Namrata, Koboldt, Daniel C., Saad, Mohamad, Wang, Bowen, Nato, Alejandro Q., Jr., Sohi, Harkirat K., Kuzma, Amanda, Wang, Li-San, Cupples, L. Adrienne, van Duijn, Cornelia, Seshadri, Sudha, Schellenberg, Gerard D., Boerwinkle, Eric, Bis, Joshua C., Dupuis, Josée, Salerno, William J., Wijsman, Ellen M., Martin, Eden R., and DeStefano, Anita L.

Published
2019
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9. Multiethnic catalog of structural variants and their translational impact for disease phenotypes across 19,652 genomes

Author

Sedlazeck, Fritz J., Yu, Bing, Mansfield, Adam J., Chen, Han, Krasheninina, Olga, Tin, Adrienne, Qi, Qibin, Zarate, Samantha, Traynelis, Joshua L., Menon, Vipin, Hu, Jianhong, Doddapaneni, Harsha, Metcalf, Ginger A., Coresh, Josef, Kaplan, Robert C., Muzny, Donna M., Jun, Goo, Gibbs, Richard A., Salerno, William J., and Boerwinkle, Eric

Subjects
0303 health sciences, education.field_of_study, Population, Disease, Computational biology, Biology, Phenotype, Genome, DNA sequencing, Genetic architecture, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Endophenotype, education, Gene, 030304 developmental biology
Abstract

Genome sequencing at population scale provides unprecedented access to the genetic foundations of human phenotypic diversity, but genotype-phenotype association analyses limited to small variants have failed to comprehensively characterize the genetic architecture of human health and disease because they ignore structural variants (SVs) known to contribute to phenotypic variation and pathogenic conditions1–3. Here we demonstrate the significance of SVs when assessing genotype-phenotype associations and the importance of ethnic diversity in study design by analyzing SVs across 19,652 individuals and the translational impact on 4,156 aptamerbased proteomic measurements across 4,021 multi-ethnic samples. The majority of 304,533 SVs detected are rare, although we identified 2,336 protein-coding genes impacted by common SVs.\We identified 64 significant SV-protein associations that comprise 36 cis- and 28 trans-acting relationships, and 21 distinct SV regions overlapped with genome-wide association study loci. These findings represent a more comprehensive mapping of regulatory and translational endophenotypes underlying health and disease.

Published
2020
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12. Parliament2: Accurate structural variant calling at scale

Author

Zarate, Samantha, primary, Carroll, Andrew, additional, Mahmoud, Medhat, additional, Krasheninina, Olga, additional, Jun, Goo, additional, Salerno, William J, additional, Schatz, Michael C, additional, Boerwinkle, Eric, additional, Gibbs, Richard A, additional, and Sedlazeck, Fritz J, additional

Published
2020
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19. O3‐06‐01: WHOLE EXOME SEQUENCING STUDY IDENTIFIES RARE COPY NUMBER VARIATIONS FOR LATE‐ONSET ALZHEIMER'S DISEASE: THE ALZHEIMER'S DISEASE SEQUENCING PROJECT CASE‐CONTROL ANALYSIS

Author

Jian, Xueqiu, primary, Chiang, Theodore, additional, Worley, Kim C., additional, Bis, Joshua C., additional, Destefano, Anita L., additional, Seshadri, Sudha, additional, Boerwinkle, Eric, additional, Fornage, Myriam, additional, and Salerno, William J., additional

Published
2018
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20. P4‐044: THE GCAD CLOUD‐BASED WORKFLOW FOR PROCESSING WHOLE EXOME AND WHOLE GENOME DATA FROM THE ALZHEIMER'S DISEASE SEQUENCING PROJECT

Author

Gangadharan, Prabhakaran, primary, Leung, Yuk Yee, additional, Valladares, Otto, additional, Chou, Yi-Fan, additional, Kuzma, Amanda B., additional, Cantwell, Laura B., additional, Qu, Liming, additional, Lin, Han-Jen, additional, Zhao, Yi, additional, Malamon, John Stephen, additional, Naj, Adam C., additional, Salerno, William J., additional, Schellenberg, Gerard D., additional, and Wang, Li-San, additional

Published
2018
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24. Exome sequencing and characterization of 49,960 individuals in the UK Biobank

Author

Van Hout, Cristopher V., Tachmazidou, Ioanna, Backman, Joshua D., Hoffman, Joshua D., Liu, Daren, Pandey, Ashutosh K., Gonzaga-Jauregui, Claudia, Khalid, Shareef, Ye, Bin, Banerjee, Nilanjana, Li, Alexander H., O’Dushlaine, Colm, Marcketta, Anthony, Staples, Jeffrey, Schurmann, Claudia, Hawes, Alicia, Maxwell, Evan, Barnard, Leland, Lopez, Alexander, Penn, John, Habegger, Lukas, Blumenfeld, Andrew L., Bai, Xiaodong, O’Keeffe, Sean, Yadav, Ashish, Praveen, Kavita, Jones, Marcus, Salerno, William J., Chung, Wendy K., Surakka, Ida, Willer, Cristen J., Hveem, Kristian, Leader, Joseph B., Carey, David J., Ledbetter, David H., Cardon, Lon, Yancopoulos, George D., Economides, Aris, Coppola, Giovanni, Shuldiner, Alan R., Balasubramanian, Suganthi, Cantor, Michael, Nelson, Matthew R., Whittaker, John, Reid, Jeffrey G., Marchini, Jonathan, Overton, John D., Scott, Robert A., Abecasis, Gonçalo R., Yerges-Armstrong, Laura, and Baras, Aris

Abstract

The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1on varicose veins, COL6A1on corneal resistance, MEPEon bone density, and IQGAP2and GMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1and BRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

Published
2020
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25. Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation

Author

Bis, Joshua C., Jian, Xueqiu, Kunkle, Brian W., Chen, Yuning, Hamilton-Nelson, Kara L., Bush, William S., Salerno, William J., Lancour, Daniel, Ma, Yiyi, Renton, Alan E., Marcora, Edoardo, Farrell, John J., Zhao, Yi, Qu, Liming, Ahmad, Shahzad, Amin, Najaf, Amouyel, Philippe, Beecham, Gary W., Below, Jennifer E., Campion, Dominique, Cantwell, Laura, Charbonnier, Camille, Chung, Jaeyoon, Crane, Paul K., Cruchaga, Carlos, Cupples, L. Adrienne, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Fulton, Lucinda, Gabriel, Stacey B., Genin, Emmanuelle, Gibbs, Richard A., Goate, Alison, Grenier-Boley, Benjamin, Gupta, Namrata, Haines, Jonathan L., Havulinna, Aki S., Helisalmi, Seppo, Hiltunen, Mikko, Howrigan, Daniel P., Ikram, M. Arfan, Kaprio, Jaakko, Konrad, Jan, Kuzma, Amanda, Lander, Eric S., Lathrop, Mark, Lehtimäki, Terho, Lin, Honghuang, Mattila, Kari, Mayeux, Richard, Muzny, Donna M., Nasser, Waleed, Neale, Benjamin, Nho, Kwangsik, Nicolas, Gaël, Patel, Devanshi, Pericak-Vance, Margaret A., Perola, Markus, Psaty, Bruce M., Quenez, Olivier, Rajabli, Farid, Redon, Richard, Reitz, Christiane, Remes, Anne M., Salomaa, Veikko, Sarnowski, Chloe, Schmidt, Helena, Schmidt, Michael, Schmidt, Reinhold, Soininen, Hilkka, Thornton, Timothy A., Tosto, Giuseppe, Tzourio, Christophe, van der Lee, Sven J., van Duijn, Cornelia M., Valladares, Otto, Vardarajan, Badri, Wang, Li-San, Wang, Weixin, Wijsman, Ellen, Wilson, Richard K., Witten, Daniela, Worley, Kim C., Zhang, Xiaoling, Bellenguez, Celine, Lambert, Jean-Charles, Kurki, Mitja I., Palotie, Aarno, Daly, Mark, Boerwinkle, Eric, Lunetta, Kathryn L., Destefano, Anita L., Dupuis, Josée, Martin, Eden R., Schellenberg, Gerard D., Seshadri, Sudha, Naj, Adam C., Fornage, Myriam, and Farrer, Lindsay A.

Abstract

The Alzheimer’s Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOEbased risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3(p = 9.8 × 10−7), an immunoglobulin gene whose antibodies interact with β-amyloid, a long non-coding RNA AC099552.4(p = 1.2 × 10−7), and a zinc-finger protein ZNF655(gene-based p = 5.0 × 10−6). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.

Published
2020
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28. THE ALZHEIMER’S DISEASE SEQUENCING PROJECT (ADSP) DATA UPDATE 2018

Author

Kuzma, Amanda B., Faber, Kelley, Salerno, William J., Leung, Yuk Yee, Cantwell, Laura B., Gupta, Namrata, Fulton, Robert, Valladares, Otto, Vogel, Briana, Appelbaum, Elizabeth, Choi, Seung Hoan, Hamilton-Nelson, Kara L., Zhao, Yi, Muzny, Donna, Qu, Liming, Reyes-Dumeyer, Dolly, Waligorski, Jason, Farrell, John, Naj, Adam C., Bis, Joshua C., Destefano, Anita L., Seshadri, Sudha, Boerwinkle, Eric, Schellenberg, Gerard, Foroud, Tatiana M., and Wang, Li-San

Published
2018
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29. Assessing structural variation in a personal genome—towards a human reference diploid genome

Author

English, Adam C, primary, Salerno, William J, additional, Hampton, Oliver A, additional, Gonzaga-Jauregui, Claudia, additional, Ambreth, Shruthi, additional, Ritter, Deborah I, additional, Beck, Christine R, additional, Davis, Caleb F, additional, Dahdouli, Mahmoud, additional, Ma, Singer, additional, Carroll, Andrew, additional, Veeraraghavan, Narayanan, additional, Bruestle, Jeremy, additional, Drees, Becky, additional, Hastie, Alex, additional, Lam, Ernest T, additional, White, Simon, additional, Mishra, Pamela, additional, Wang, Min, additional, Han, Yi, additional, Zhang, Feng, additional, Stankiewicz, Pawel, additional, Wheeler, David A, additional, Reid, Jeffrey G, additional, Muzny, Donna M, additional, Rogers, Jeffrey, additional, Sabo, Aniko, additional, Worley, Kim C, additional, Lupski, James R, additional, Boerwinkle, Eric, additional, and Gibbs, Richard A, additional

Published
2015
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30. Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation

Author

Bis, Joshua C., Jian, Xueqiu, Kunkle, Brian W., Chen, Yuning, Hamilton-Nelson, Kara L., Bush, William S., Salerno, William J., Lancour, Daniel, Ma, Yiyi, Renton, Alan E., Marcora, Edoardo, Farrell, John J., Zhao, Yi, Qu, Liming, Ahmad, Shahzad, Amin, Najaf, Amouyel, Philippe, Beecham, Gary W., Below, Jennifer E., Campion, Dominique, Cantwell, Laura, Charbonnier, Camille, Chung, Jaeyoon, Crane, Paul K., Cruchaga, Carlos, Cupples, L. Adrienne, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Fulton, Lucinda, Gabriel, Stacey B., Genin, Emmanuelle, Gibbs, Richard A., Goate, Alison, Grenier-Boley, Benjamin, Gupta, Namrata, Haines, Jonathan L., Havulinna, Aki S., Helisalmi, Seppo, Hiltunen, Mikko, Howrigan, Daniel P., Ikram, M. Arfan, Kaprio, Jaakko, Konrad, Jan, Kuzma, Amanda, Lander, Eric S., Lathrop, Mark, Lehtimäki, Terho, Lin, Honghuang, Mattila, Kari, Mayeux, Richard, Muzny, Donna M., Nasser, Waleed, Neale, Benjamin, Nho, Kwangsik, Nicolas, Gaël, Patel, Devanshi, Pericak-Vance, Margaret A., Perola, Markus, Psaty, Bruce M., Quenez, Olivier, Rajabli, Farid, Redon, Richard, Reitz, Christiane, Remes, Anne M., Salomaa, Veikko, Sarnowski, Chloe, Schmidt, Helena, Schmidt, Michael, Schmidt, Reinhold, Soininen, Hilkka, Thornton, Timothy A., Tosto, Giuseppe, Tzourio, Christophe, van der Lee, Sven J., van Duijn, Cornelia M., Valladares, Otto, Vardarajan, Badri, Wang, Li-San, Wang, Weixin, Wijsman, Ellen, Wilson, Richard K., Witten, Daniela, Worley, Kim C., Zhang, Xiaoling, Bellenguez, Celine, Lambert, Jean-Charles, Kurki, Mitja I., Palotie, Aarno, Daly, Mark, Boerwinkle, Eric, Lunetta, Kathryn L., Destefano, Anita L., Dupuis, Josée, Martin, Eden R., Schellenberg, Gerard D., Seshadri, Sudha, Naj, Adam C., Fornage, Myriam, and Farrer, Lindsay A.

Abstract

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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32. P1‐149: THE ALZHEIMER'S DISEASE SEQUENCING PROJECT (ADSP) DATA UPDATE 2018.

Author

Kuzma, Amanda B., Faber, Kelley, Salerno, William J., Leung, Yuk Yee, Cantwell, Laura B., Gupta, Namrata, Fulton, Robert, Valladares, Otto, Vogel, Briana, Appelbaum, Elizabeth, Choi, Seung Hoan, Hamilton-Nelson, Kara L., Zhao, Yi, Muzny, Donna, Qu, Liming, Reyes-Dumeyer, Dolly, Waligorski, Jason, Farrell, John, Naj, Adam C., and Bis, Joshua C.

Published
2018
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33. Structural variation across 138,134 samples in the TOPMed consortium.

Author

Jun G, English AC, Metcalf GA, Yang J, Chaisson MJ, Pankratz N, Menon VK, Salerno WJ, Krasheninina O, Smith AV, Lane JA, Blackwell T, Kang HM, Salvi S, Meng Q, Shen H, Pasham D, Bhamidipati S, Kottapalli K, Arnett DK, Ashley-Koch A, Auer PL, Beutel KM, Bis JC, Blangero J, Bowden DW, Brody JA, Cade BE, Chen YI, Cho MH, Curran JE, Fornage M, Freedman BI, Fingerlin T, Gelb BD, Hou L, Hung YJ, Kane JP, Kaplan R, Kim W, Loos RJF, Marcus GM, Mathias RA, McGarvey ST, Montgomery C, Naseri T, Nouraie SM, Preuss MH, Palmer ND, Peyser PA, Raffield LM, Ratan A, Redline S, Reupena S, Rotter JI, Rich SS, Rienstra M, Ruczinski I, Sankaran VG, Schwartz DA, Seidman CE, Seidman JG, Silverman EK, Smith JA, Stilp A, Taylor KD, Telen MJ, Weiss ST, Williams LK, Wu B, Yanek LR, Zhang Y, Lasky-Su J, Gingras MC, Dutcher SK, Eichler EE, Gabriel S, Germer S, Kim R, Viaud-Martinez KA, Nickerson DA, Luo J, Reiner A, Gibbs RA, Boerwinkle E, Abecasis G, and Sedlazeck FJ

Abstract

Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34% novel) across autosomes and the X chromosome (50bp+) from 138,134 individuals in the diverse TOPMed consortium. We describe our methodologies for SV inference resulting in high variant quality and >90% allele concordance compared to long-read de-novo assemblies of well-characterized control samples. We demonstrate utility through significant associations between SVs and important various cardio-metabolic and hematologic traits. We have identified 690 SV hotspots and deserts and those that potentially impact the regulation of medically relevant genes. This catalog characterizes SVs across multiple populations and will serve as a valuable tool to understand the impact of SV on disease development and progression.

Published
2023
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34. Sparse Project VCF: efficient encoding of population genotype matrices.

Author

Lin MF, Bai X, Salerno WJ, and Reid JG

Subjects
Base Sequence, Genotype, Germ Cells, Genomics, Software
Abstract

Summary: Variant Call Format (VCF), the prevailing representation for germline genotypes in population sequencing, suffers rapid size growth as larger cohorts are sequenced and more rare variants are discovered. We present Sparse Project VCF (spVCF), an evolution of VCF with judicious entropy reduction and run-length encoding, delivering >10× size reduction for modern studies with practically minimal information loss. spVCF interoperates with VCF efficiently, including tabix-based random access. We demonstrate its effectiveness with the DiscovEHR and UK Biobank whole-exome sequencing cohorts., Availability and Implementation: Apache-licensed reference implementation: github.com/mlin/spVCF., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

Published
2021
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