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2. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

Author

Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N, Wielscher, Matthias, Geller, Frank, Juodakis, Julius, Mahajan, Anubha, Bradfield, Jonathan P, Lin, Frederick TJ, Vogelezang, Suzanne, Bustamante, Mariona, Ahluwalia, Tarunveer S, Pitkänen, Niina, Wang, Carol A, Bacelis, Jonas, Borges, Maria C, Zhang, Ge, Bedell, Bruce A, Rossi, Robert M, Skogstrand, Kristin, Peng, Shouneng, Thompson, Wesley K, Appadurai, Vivek, Lawlor, Debbie A, Kalliala, Ilkka, Power, Christine, McCarthy, Mark I, Boyd, Heather A, Marazita, Mary L, Hakonarson, Hakon, Hayes, M Geoffrey, Scholtens, Denise M, Rivadeneira, Fernando, Jaddoe, Vincent WV, Vinding, Rebecca K, Bisgaard, Hans, Knight, Bridget A, Pahkala, Katja, Raitakari, Olli, Helgeland, Øyvind, Johansson, Stefan, Njølstad, Pål R, Fadista, João, Schork, Andrew J, Nudel, Ron, Miller, Daniel E, Chen, Xiaoting, Weirauch, Matthew T, Mortensen, Preben Bo, Børglum, Anders D, Nordentoft, Merete, Mors, Ole, Hao, Ke, Ryckman, Kelli K, Hougaard, David M, Kottyan, Leah C, Pennell, Craig E, Lyytikainen, Leo-Pekka, Bønnelykke, Klaus, Vrijheid, Martine, Felix, Janine F, Lowe, William L, Grant, Struan FA, Hyppönen, Elina, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Muglia, Louis J, Murray, Jeffrey C, Freathy, Rachel M, Werge, Thomas M, Melbye, Mads, Buil, Alfonso, and Feenstra, Bjarke

Subjects
Chromosomes, Human, Pair 2, Fetus, Humans, Premature Birth, Cytokines, Gestational Age, Pregnancy, Polymorphism, Single Nucleotide, Genome, Human, Infant, Newborn, Female, Genome-Wide Association Study, Chromosomes, Human, Pair 2, Polymorphism, Single Nucleotide, Genome, Infant, Newborn
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Published
2019

3. Fish Oil Supplementation in Pregnancy and Neurodevelopment in Childhood--A Randomized Clinical Trial

Author

Sass, Laerke, Bjarnadóttir, Elín, Stokholm, Jakob, Chawes, Bo, Vinding, Rebecca K., Mora-Jensen, Anna-Rosa C., Thorsen, Jonathan, Noergaard, Sarah, Ebdrup, Bjørn H., Jepsen, Jens R.M, Fagerlund, Birgitte, Bønnelykke, Klaus, Lauritzen, Lotte, and Bisgaard, Hans

Abstract

A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC[subscript 2010] mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.

Published
2021
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4. Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

Author

Zheng, Yan, Huang, Tao, Wang, Tiange, Mei, Zhendong, Sun, Zhonghan, Zhang, Tao, Ellervik, Christina, Chai, Jin-Fang, Sim, Xueling, van Dam, Rob M., Tai, E-Shyong, Koh, Woon-Puay, Dorajoo, Rajkumar, Saw, Seang-Mei, Sabanayagam, Charumathi, Wong, Tien Yin, Gupta, Preeti, Rossing, Peter, Ahluwalia, Tarunveer S., Vinding, Rebecca K., Bisgaard, Hans, Bønnelykke, Klaus, Wang, Yujie, Graff, Mariaelisa, Voortman, Trudy, van Rooij, Frank J. A., Hofman, Albert, van Heemst, Diana, Noordam, Raymond, Estampador, Angela C., Varga, Tibor V., Enzenbach, Cornelia, Scholz, Markus, Thiery, Joachim, Burkhardt, Ralph, Orho-Melander, Marju, Schulz, Christina-Alexandra, Ericson, Ulrika, Sonestedt, Emily, Kubo, Michiaki, Akiyama, Masato, Zhou, Ang, Kilpeläinen, Tuomas O., Hansen, Torben, Kleber, Marcus E., Delgado, Graciela, McCarthy, Mark, Lemaitre, Rozenn N., Felix, Janine F., Jaddoe, Vincent W. V., Wu, Ying, Mohlke, Karen L., Lehtimäki, Terho, Wang, Carol A., Pennell, Craig E., Schunkert, Heribert, Kessler, Thorsten, Zeng, Lingyao, Willenborg, Christina, Peters, Annette, Lieb, Wolfgang, Grote, Veit, Rzehak, Peter, Koletzko, Berthold, Erdmann, Jeanette, Munz, Matthias, Wu, Tangchun, He, Meian, Yu, Caizheng, Lecoeur, Cécile, Froguel, Philippe, Corella, Dolores, Moreno, Luis A., Lai, Chao-Qiang, Pitkänen, Niina, Boreham, Colin A., Ridker, Paul M., Rosendaal, Frits R., de Mutsert, Renée, Power, Chris, Paternoster, Lavinia, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Djousse, Luc, Rivadeneira, Fernando, Lee, Nanette R., Raitakari, Olli T., Kähönen, Mika, Viikari, Jorma, Langhendries, Jean-Paul, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, König, Inke, Balkau, Beverley, Coltell, Oscar, Dallongeville, Jean, Meirhaeghe, Aline, Amouyel, Philippe, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, März, Winfried, Mackey, David A., Gruszfeld, Dariusz, Tucker, Katherine L., Fumeron, Frédéric, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., North, Kari E., Chasman, Daniel I., and Qi, Lu

Published
2020

6. Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial

Author

Stokholm, Jakob, Chawes, Bo L, Vissing, Nadja H, Bjarnadóttir, Elín, Pedersen, Tine M, Vinding, Rebecca K, Schoos, Ann-Marie M, Wolsk, Helene M, Thorsteinsdóttir, Sunna, Hallas, Henrik W, Arianto, Lambang, Schjørring, Susanne, Krogfelt, Karen A, Fischer, Thea K, Pipper, Christian B, Bønnelykke, Klaus, and Bisgaard, Hans

Published
2016
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10. Association between childhood asthma and attention deficit hyperactivity or autism spectrum disorders:A systematic review with meta-analysis

Author

Kaas, Trine H, Vinding, Rebecca K, Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, Chawes, Bo L, Kaas, Trine H, Vinding, Rebecca K, Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, and Chawes, Bo L

Abstract

BACKGROUND: Children with asthma are at risk of depression and anxiety and growing evidence suggest they may also be at risk of attention deficit hyperreactivity disorder (ADHD) and autism spectrum disorder (ASD). Here, we conducted a systematic review with meta-analysis of studies investigating association between asthma and ADHD or ASD in children.METHODS: A comprehensive search using PubMed, EMBASE and Cochrane Library databases was completed in March 2019. Observational human studies published in English, clinic-based or population-based with a healthy comparator group, evaluating asthma-ADHD or asthma-ASD overlap in children 18 years or younger using categorical diagnoses (yes/no) were considered for inclusion. Random effects meta-analysis models were used to analyse data. The Newcastle Ottawa Scale was used to evaluate risk of bias.RESULTS: A total of 25 asthma-ADHD studies were included of which 17 showed significant positive associations and one a negative association: 17/25 studies were population-based, 19/25 were cross-sectional or cohort studies and 7/25 had a low risk of bias. We performed a meta-analysis of 23 of the studies, which showed a significant association between asthma and ADHD: odds ratio (OR) 1.52 (1.42-1.63), P < .001, I2 = 60%. All studies were adjusted for age and sex and a large proportion; that is, 19/23 were further adjusted for relevant confounders. Seventeen asthma-ASD studies were included, whereof 7 showed a positive association and 3 a negative association; 8/17 were population-based with a cross-sectional study design and 4/17 had a low risk of bias. We performed a meta-analysis of 14 of the studies, which did not show a significant association between asthma and ASD: OR 1.12 (0.93-1.34), P = .24, I2 = 89%. All studies were adjusted for age and sex and 10/14 were further adjusted for relevant confounders.CONCLUSIONS: This systematic review with meta-analyses shows a significant overlap between asthma a

Published
2021

11. Novel Loci for Childhood Body Mass Index and Shared Heritability with Adult Cardiometabolic Traits

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkanen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Oyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao Catalá, José Ramón, Schnurr, Theresia M., Barroso, Ines, Bonnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie Aline, Chawes, Bo, Clement, Karine, Closa Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquín, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke Jan, Hypponen, Elina, Johansson, Stefan, Joro, Raimo, Kahonen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kuehnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimaki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina Gómez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, Andre G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa Marina, Loreto, Reischl, Eva, Frithioff-Bojsoe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njolstad, Pal R., Dedoussis, George D., Froguel, Philippe, Sorensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikainen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widen, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Jarvelin, Marjo-Riitta, Koerner, Antje, Smith, George Davey, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Jaddoe, Vincent W. V., Grant, Struan F. A., Felix, Janine F., Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkanen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Oyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao Catalá, José Ramón, Schnurr, Theresia M., Barroso, Ines, Bonnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie Aline, Chawes, Bo, Clement, Karine, Closa Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquín, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke Jan, Hypponen, Elina, Johansson, Stefan, Joro, Raimo, Kahonen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kuehnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimaki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina Gómez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, Andre G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa Marina, Loreto, Reischl, Eva, Frithioff-Bojsoe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njolstad, Pal R., Dedoussis, George D., Froguel, Philippe, Sorensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikainen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widen, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Jarvelin, Marjo-Riitta, Koerner, Antje, Smith, George Davey, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Jaddoe, Vincent W. V., Grant, Struan F. A., and Felix, Janine F.

Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. O

Published
2020

12. Effect of High-Dose vs Standard-Dose Vitamin D Supplementation in Pregnancy on Bone Mineralization in Offspring Until Age 6 Years:A Prespecified Secondary Analysis of a Double-Blinded, Randomized Clinical Trial

Author

Brustad, Nicklas, Garland, Juri, Thorsen, Jonathan, Sevelsted, Astrid, Krakauer, Martin, Vinding, Rebecca K, Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, Chawes, Bo L, Brustad, Nicklas, Garland, Juri, Thorsen, Jonathan, Sevelsted, Astrid, Krakauer, Martin, Vinding, Rebecca K, Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, and Chawes, Bo L

Abstract

Importance: Studies suggest an association between maternal vitamin D status during pregnancy and offspring anthropometry and bone mineralization, but investigations are few and with mixed results.Objective: To investigate the effect of a high dose vs standard dose of vitamin D supplementation in pregnancy on anthropometric and bone outcomes until age 6 years in the offspring.Design, Setting, and Participants: A prespecified analysis of a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort that included 623 pregnant mothers and their 584 children. Data were analyzed between January 2019 and September 2019.Interventions: Vitamin D supplementation of 2800 IU/d (high-dose) vs 400 IU/d (standard-dose) from pregnancy week 24 until 1 week after birth.Main Outcomes and Measures: Longitudinal anthropometry assessments including length/height, weight, and body mass index until age 6 years and bone mineral content (BMC) and bone mineral density (BMD) at age 3 years and 6 years from dual-energy radiography absorptiometry scans.Results: At age 6 years, 517 children (89%) completed the clinical follow-up. All participants were Danish and white; 261 were boys and 256 were girls. A mixed-effects model analysis of dual-energy radiography absorptiometry scan outcomes from ages 3 years and 6 years showed that children in the vitamin D vs placebo group had higher whole-body BMC: mean difference adjusted (aMD) for age, sex, height, and weight was 11.5 g (95% CI, 2.3-20.7; P = .01); higher whole-body-less-head BMC aMD was 7.5 g (95% CI, 1.5-13.5; P = .01); and higher head BMD aMD was 0.023 g/cm2 (95% CI, 0.003-0.004; P = .03). The largest effect was in children from vitamin D-insufficient mothers (<30 ng/mL; to convert to nanomoles per liter, multiply by 2.496) and among winter births. In a post hoc analysis, we found borderline lower incidence of fractures in the vitamin

Published
2020

14. Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis

Author

van Rossem, Lenie, primary, Smit, Henriette A., additional, Armand, Martine, additional, Bernard, Jonathan Y., additional, Bisgaard, Hans, additional, Bønnelykke, Klaus, additional, Bruun, Signe, additional, Heude, Barbara, additional, Husby, Steffen, additional, Kyhl, Henriette B., additional, Michaelsen, Kim F., additional, Stark, Ken D., additional, Thijs, Carel, additional, Vinding, Rebecca K., additional, Wijga, Alet H., additional, and Lauritzen, Lotte, additional

Published
2020
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16. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, Freathy, Rachel M, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, and Freathy, Rachel M

Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019

17. Maturation of the gut microbiome and risk of asthma in childhood

Author

Stokholm, Jakob, Blaser, Martin J., Thorsen, Jonathan, Rasmussen, Morten Arendt, Waage, Johannes Eichler, Vinding, Rebecca K., Schoos, Ann-Marie Malby, Kunøe, Asja, Fink, Nadia R., Chawes, Bo L., Bønnelykke, Klaus, Brejnrod, Asker Daniel, Mortensen, Martin Steen, Abu Al-Soud, Waleed, Sørensen, Søren Johannes, Bisgaard, Hans, Stokholm, Jakob, Blaser, Martin J., Thorsen, Jonathan, Rasmussen, Morten Arendt, Waage, Johannes Eichler, Vinding, Rebecca K., Schoos, Ann-Marie Malby, Kunøe, Asja, Fink, Nadia R., Chawes, Bo L., Bønnelykke, Klaus, Brejnrod, Asker Daniel, Mortensen, Martin Steen, Abu Al-Soud, Waleed, Sørensen, Søren Johannes, and Bisgaard, Hans

Published
2018

18. Association between childhood asthma and attention deficit hyperactivity or autism spectrum disorders: A systematic review with meta‐analysis.

Author

Kaas, Trine H., Vinding, Rebecca K., Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, and Chawes, Bo L.

Subjects
*ASTHMA in children, *AUTISM spectrum disorders, *MEDICAL personnel, *RANDOM effects model, *ATTENTION-deficit hyperactivity disorder, *YOUTH with attention-deficit hyperactivity disorder
Abstract

Background: Children with asthma are at risk of depression and anxiety and growing evidence suggest they may also be at risk of attention deficit hyperreactivity disorder (ADHD) and autism spectrum disorder (ASD). Here, we conducted a systematic review with meta‐analysis of studies investigating association between asthma and ADHD or ASD in children. Methods: A comprehensive search using PubMed, EMBASE and Cochrane Library databases was completed in March 2019. Observational human studies published in English, clinic‐based or population‐based with a healthy comparator group, evaluating asthma‐ADHD or asthma‐ASD overlap in children 18 years or younger using categorical diagnoses (yes/no) were considered for inclusion. Random effects meta‐analysis models were used to analyse data. The Newcastle Ottawa Scale was used to evaluate risk of bias. Results: A total of 25 asthma‐ADHD studies were included of which 17 showed significant positive associations and one a negative association: 17/25 studies were population‐based, 19/25 were cross‐sectional or cohort studies and 7/25 had a low risk of bias. We performed a meta‐analysis of 23 of the studies, which showed a significant association between asthma and ADHD: odds ratio (OR) 1.52 (1.42‐1.63), P <.001, I2 = 60%. All studies were adjusted for age and sex and a large proportion; that is, 19/23 were further adjusted for relevant confounders. Seventeen asthma‐ASD studies were included, whereof 7 showed a positive association and 3 a negative association; 8/17 were population‐based with a cross‐sectional study design and 4/17 had a low risk of bias. We performed a meta‐analysis of 14 of the studies, which did not show a significant association between asthma and ASD: OR 1.12 (0.93‐1.34), P =.24, I2 = 89%. All studies were adjusted for age and sex and 10/14 were further adjusted for relevant confounders. Conclusions: This systematic review with meta‐analyses shows a significant overlap between asthma and ADHD, but not between asthma and ASD in children. Clinicians taking care of children with asthma or ADHD should be aware of such association to aid an early diagnosis and treatment of such comorbidity. [ABSTRACT FROM AUTHOR]

Published
2021
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19. Publisher Correction: Maturation of the gut microbiome and risk of asthma in childhood

Author

Stokholm, Jakob, primary, Blaser, Martin J., additional, Thorsen, Jonathan, additional, Rasmussen, Morten A., additional, Waage, Johannes, additional, Vinding, Rebecca K., additional, Schoos, Ann-Marie M., additional, Kunøe, Asja, additional, Fink, Nadia R., additional, Chawes, Bo L., additional, Bønnelykke, Klaus, additional, Brejnrod, Asker D., additional, Mortensen, Martin S., additional, Al-Soud, Waleed Abu, additional, Sørensen, Søren J., additional, and Bisgaard, Hans, additional

Published
2018
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20. Maturation of the gut microbiome and risk of asthma in childhood

Author

Stokholm, Jakob, primary, Blaser, Martin J., additional, Thorsen, Jonathan, additional, Rasmussen, Morten A., additional, Waage, Johannes, additional, Vinding, Rebecca K., additional, Schoos, Ann-Marie M., additional, Kunøe, Asja, additional, Fink, Nadia R., additional, Chawes, Bo L., additional, Bønnelykke, Klaus, additional, Brejnrod, Asker D., additional, Mortensen, Martin S., additional, Al-Soud, Waleed Abu, additional, Sørensen, Søren J., additional, and Bisgaard, Hans, additional

Published
2018
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21. Fish Oil–Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

Author

Bisgaard, Hans, primary, Stokholm, Jakob, additional, Chawes, Bo L., additional, Vissing, Nadja H., additional, Bjarnadóttir, Elin, additional, Schoos, Ann-Marie M., additional, Wolsk, Helene M., additional, Pedersen, Tine M., additional, Vinding, Rebecca K., additional, Thorsteinsdóttir, Sunna, additional, Følsgaard, Nilofar V., additional, Fink, Nadia R., additional, Thorsen, Jonathan, additional, Pedersen, Anders G., additional, Waage, Johannes, additional, Rasmussen, Morten A., additional, Stark, Ken D., additional, Olsen, Sjurdur F., additional, and Bønnelykke, Klaus, additional

Published
2016
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22. Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring:a randomized clinical trial

Author

Chawes, Bo Lund Krogsgaard, Bønnelykke, Klaus, Stokholm, Jakob, Vissing, Nadja H., Bjarnadóttir, Elín, Schoos, Ann-Marie Malby, Wolsk, Helene M., Pedersen, Tine Marie, Vinding, Rebecca K., Thorsteinsdóttir, Sunna, Arianto, Lambang, Hallas, Henrik Wegener, Heickendorff, Lene, Pedersen, Susanne Brix, Rasmussen, Morten Arendt, Bisgaard, Hans, Chawes, Bo Lund Krogsgaard, Bønnelykke, Klaus, Stokholm, Jakob, Vissing, Nadja H., Bjarnadóttir, Elín, Schoos, Ann-Marie Malby, Wolsk, Helene M., Pedersen, Tine Marie, Vinding, Rebecca K., Thorsteinsdóttir, Sunna, Arianto, Lambang, Hallas, Henrik Wegener, Heickendorff, Lene, Pedersen, Susanne Brix, Rasmussen, Morten Arendt, and Bisgaard, Hans

Published
2016

23. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years:a randomised, double-blind, placebo-controlled trial

Author

Stokholm, Jakob, Chawes, Bo L, Vissing, Nadja H, Bjarnadóttir, Elín, Pedersen, Tine M, Vinding, Rebecca K, Schoos, Ann-Marie M, Wolsk, Helene M, Thorsteinsdóttir, Sunna, Hallas, Henrik W, Arianto, Lambang, Schjørring, Susanne, Krogfelt, Karen A, Fischer, Thea K, Pipper, Christian B, Bønnelykke, Klaus, Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo L, Vissing, Nadja H, Bjarnadóttir, Elín, Pedersen, Tine M, Vinding, Rebecca K, Schoos, Ann-Marie M, Wolsk, Helene M, Thorsteinsdóttir, Sunna, Hallas, Henrik W, Arianto, Lambang, Schjørring, Susanne, Krogfelt, Karen A, Fischer, Thea K, Pipper, Christian B, Bønnelykke, Klaus, and Bisgaard, Hans

Abstract

BACKGROUND: Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period.METHODS: In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297.FINDINGS: Between Nov 17, 20

Published
2016

24. Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

Author

Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo L., Vissing, Nadja H., Bjarnadóttir, Elin, Schoos, Ann-Marie M., Wolsk, Helene M, Vinding, Rebecca K., Thorsteinsdóttir, Sunna, Følsgaard, Nilofar V., Fink, Nadia R., Thorsen, Jonathan, Pedersen, Anders Gorm, Waage, Johannes, Rasmussen, Morten A., Stark, Ken D., Olsen, Sjurdur F., Bønnelykke, Klaus, Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo L., Vissing, Nadja H., Bjarnadóttir, Elin, Schoos, Ann-Marie M., Wolsk, Helene M, Vinding, Rebecca K., Thorsteinsdóttir, Sunna, Følsgaard, Nilofar V., Fink, Nadia R., Thorsen, Jonathan, Pedersen, Anders Gorm, Waage, Johannes, Rasmussen, Morten A., Stark, Ken D., Olsen, Sjurdur F., and Bønnelykke, Klaus

Abstract

Background: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods: We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. Results: A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically sig

Published
2016

25. Effect of Vitamin D3Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring

Author

Chawes, Bo L., primary, Bønnelykke, Klaus, additional, Stokholm, Jakob, additional, Vissing, Nadja H., additional, Bjarnadóttir, Elín, additional, Schoos, Ann-Marie M., additional, Wolsk, Helene M., additional, Pedersen, Tine Marie, additional, Vinding, Rebecca K., additional, Thorsteinsdóttir, Sunna, additional, Arianto, Lambang, additional, Hallas, Henrik W., additional, Heickendorff, Lene, additional, Brix, Susanne, additional, Rasmussen, Morten A., additional, and Bisgaard, Hans, additional

Published
2016
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26. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M., Beaumont, Robin N., Horikoshi, Momoko, Day, Felix R., Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R., Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R., Rayner, N. William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J., Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M., Zafarmand, Mohammad H., Bradfield, Jonathan P., Grarup, Niels, Kooijman, Marjolein N., Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S., Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L., Wu, Ying, Thiering, Elisabeth, Wang, Carol A., Have, Christian T., Vilor-Tejedor, Natalia, Joshi, Peter K., Painter, Jodie N., Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M., Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C., Espinosa, Ana, Barton, Sheila J., Inskip, Hazel M., Holloway, John W., Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A., Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L., Murabito, Joanne M., Relton, Caroline L., Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J., Heikkinen, Jani, Morgen, Camilla S., van Kampen, Antoine H. C., van Schaik, Barbera D. C., Mentch, Frank D., Langenberg, Claudia, Luan, Jian’an, Scott, Robert A., Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M., Bennett, Amanda J., Gaulton, Kyle J., Fernandez-Tajes, Juan, van Zuydam, Natalie R., Medina-Gomez, Carolina, de Haan, Hugoline G., Rosendaal, Frits R., Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V. R., Fonvig, Cilius E., Trier, Caecilie, van Beijsterveldt, Catharina E. M., Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M., Mercader, Josep M., Linneberg, Allan, Schraut, Katharina E., Lind, Penelope A., Medland, Sarah E., Shields, Beverley M., Knight, Bridget A., Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K., Willems, Sara M., Atalay, Mustafa, Chawes, Bo L., Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A., Yaghootkar, Hanieh, Ruth, Katherine S., Jones, Samuel E., Loh, Po-Ru, Murray, Anna, Weedon, Michael N., Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F., Eloranta, Aino-Maija, Lakka, Timo A., van Duijn, Cornelia M., Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T., Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V., Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W., Campbell, Harry, Wilson, James F., Vrijkotte, Tanja G. M., Vrijheid, Martine, de Geus, Eco J. C. N., Hayes, M. Geoffrey, Kadarmideen, Haja N., Holm, Jens-Christian, Beilin, Lawrence J., Pennell, Craig E., Heinrich, Joachim, Adair, Linda S., Borja, Judith B., Mohlke, Karen L., Eriksson, Johan G., Widén, Elisabeth E., Hattersley, Andrew T., Spector, Tim D., Kähönen, Mika, Viikari, Jorma S., Lehtimäki, Terho, Boomsma, Dorret I., Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I. A., Bisgaard, Hans, Bønnelykke, Klaus, Murray, Jeffrey C., Melbye, Mads, Nohr, Ellen A., Mook-Kanamori, Dennis O., Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F., Jaddoe, Vincent W. V., Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A., Pedersen, Oluf, Uitterlinden, André G., Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M., Lowe, William L., Davey Smith, George, Timpson, Nicholas J., Morris, Andrew P., Wareham, Nicholas J., Hakonarson, Hakon, Grant, Struan F. A., Frayling, Timothy M., Lawlor, Debbie A., Njølstad, Pål R., Johansson, Stefan, Ong, Ken K., McCarthy, Mark I., Perry, John R. B., Evans, David M., and Freathy, Rachel M.

Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n= 321,223) and offspring birth weight (n= 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight–blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019
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27. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Vogelezang, Suzanne, Bradfield, Jonathan P., Ahluwalia, Tarunveer S., Curtin, John A., Lakka, Timo A., Grarup, Niels, Scholz, Markus, Van Der Most, Peter J., Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O., Vilor-Tejedor, Natalia, Cousminer, Diana L., Standl, Marie, Wang, Carol A., Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkänen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Øyvind, Selzam, Saskia, Vonk, Judith M., Zafarmand, Mohammed H., Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N., Have, Christian T., Rzehak, Peter, Bilbao, Jose Ramon, Schnurr, Theresia M., Barroso, Inês, Bønnelykke, Klaus, Beilin, Lawrence J., Carstensen, Lisbeth, Charles, Marie-Aline, Chawes, Bo, Clément, Karine, Closa-Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G., Escribano, Joaquin, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T., Hollensted, Mette, Hottenga, Jouke-Jan, Hyppönen, Elina, Johansson, Stefan, Joro, Raimo, Kähönen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A., Koletzko, Berthold, Kühnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimäki, Terho, Leinonen, Jaakko T., Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina-Gomez, Carolina, Melbye, Mads, Michaelsen, Kim F., Morgen, Camilla S., Mori, Trevor A., Nielsen, Tenna R. H., Niinikoski, Harri, Oldehinkel, Albertine J., Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E., Power, Christine, Reijneveld, Sijmen A., Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D., Stokholm, Jakob, Teo, Kook K., Thiering, Elisabeth, Timpson, Nicholas J., Uitterlinden, André G., Van Beijsterveldt, Catharina E. M., Van Schaik, Barbera D. C., Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K., Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V., Brown, Christopher D., Santa-Marina, Loreto, Reischl, Eva, Frithioff-Bøjsøe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A., Vrijkotte, Tanja G. M., Koppelman, Gerard H., Plomin, Robert, Njølstad, Pål R., Dedoussis, George D., Froguel, Philippe, Sørensen, Thorkild I. A., Jacobsson, Bo, Freathy, Rachel M., Zemel, Babette S., Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikäinen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G., Heinrich, Joachim, Widén, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I., Järvelin, Marjo-Riitta, Körner, Antje, Davey Smith, George, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I., Early Growth Genetics Consortium, Jaddoe, Vincent W. V., Grant, Struan F. A., and Felix, Janine F.

Subjects
2. Zero hunger, Research and analysis methods, Physical sciences, Medicine and health sciences, Biology and life sciences, nutritional and metabolic diseases, FOS: Physical sciences, Research Article
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values

28. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Vogelezang, Suzanne, Bradfield, Jonathan P, Ahluwalia, Tarunveer S, Curtin, John A, Lakka, Timo A, Grarup, Niels, Scholz, Markus, Van Der Most, Peter J, Monnereau, Claire, Stergiakouli, Evie, Heiskala, Anni, Horikoshi, Momoko, Fedko, Iryna O, Vilor-Tejedor, Natalia, Cousminer, Diana L, Standl, Marie, Wang, Carol A, Viikari, Jorma, Geller, Frank, Íñiguez, Carmen, Pitkänen, Niina, Chesi, Alessandra, Bacelis, Jonas, Yengo, Loic, Torrent, Maties, Ntalla, Ioanna, Helgeland, Øyvind, Selzam, Saskia, Vonk, Judith M, Zafarmand, Mohammed H, Heude, Barbara, Farooqi, Ismaa Sadaf, Alyass, Akram, Beaumont, Robin N, Have, Christian T, Rzehak, Peter, Bilbao, Jose Ramon, Schnurr, Theresia M, Barroso, Inês, Bønnelykke, Klaus, Beilin, Lawrence J, Carstensen, Lisbeth, Charles, Marie-Aline, Chawes, Bo, Clément, Karine, Closa-Monasterolo, Ricardo, Custovic, Adnan, Eriksson, Johan G, Escribano, Joaquin, Groen-Blokhuis, Maria, Grote, Veit, Gruszfeld, Dariusz, Hakonarson, Hakon, Hansen, Torben, Hattersley, Andrew T, Hollensted, Mette, Hottenga, Jouke-Jan, Hyppönen, Elina, Johansson, Stefan, Joro, Raimo, Kähönen, Mika, Karhunen, Ville, Kiess, Wieland, Knight, Bridget A, Koletzko, Berthold, Kühnapfel, Andreas, Landgraf, Kathrin, Langhendries, Jean-Paul, Lehtimäki, Terho, Leinonen, Jaakko T, Li, Aihuali, Lindi, Virpi, Lowry, Estelle, Bustamante, Mariona, Medina-Gomez, Carolina, Melbye, Mads, Michaelsen, Kim F, Morgen, Camilla S, Mori, Trevor A, Nielsen, Tenna RH, Niinikoski, Harri, Oldehinkel, Albertine J, Pahkala, Katja, Panoutsopoulou, Kalliope, Pedersen, Oluf, Pennell, Craig E, Power, Christine, Reijneveld, Sijmen A, Rivadeneira, Fernando, Simpson, Angela, Sly, Peter D, Stokholm, Jakob, Teo, Kook K, Thiering, Elisabeth, Timpson, Nicholas J, Uitterlinden, André G, Van Beijsterveldt, Catharina EM, Van Schaik, Barbera DC, Vaudel, Marc, Verduci, Elvira, Vinding, Rebecca K, Vogel, Mandy, Zeggini, Eleftheria, Sebert, Sylvain, Lind, Mads V, Brown, Christopher D, Santa-Marina, Loreto, Reischl, Eva, Frithioff-Bøjsøe, Christine, Meyre, David, Wheeler, Eleanor, Ong, Ken, Nohr, Ellen A, Vrijkotte, Tanja GM, Koppelman, Gerard H, Plomin, Robert, Njølstad, Pål R, Dedoussis, George D, Froguel, Philippe, Sørensen, Thorkild IA, Jacobsson, Bo, Freathy, Rachel M, Zemel, Babette S, Raitakari, Olli, Vrijheid, Martine, Feenstra, Bjarke, Lyytikäinen, Leo-Pekka, Snieder, Harold, Kirsten, Holger, Holt, Patrick G, Heinrich, Joachim, Widén, Elisabeth, Sunyer, Jordi, Boomsma, Dorret I, Järvelin, Marjo-Riitta, Körner, Antje, Davey Smith, George, Holm, Jens-Christian, Atalay, Mustafa, Murray, Clare, Bisgaard, Hans, McCarthy, Mark I, Early Growth Genetics Consortium, Jaddoe, Vincent WV, Grant, Struan FA, and Felix, Janine F

Subjects
2. Zero hunger, Adult, Male, Menarche, Adolescent, Monosaccharide Transport Proteins, Waist-Hip Ratio, Nedd4 Ubiquitin Protein Ligases, nutritional and metabolic diseases, Cardiometabolic Risk Factors, Blood Pressure, Mendelian Randomization Analysis, 3. Good health, Body Mass Index, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Child, Preschool, Humans, Female, Genetic Predisposition to Disease, Child, Genome-Wide Association Study
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values

29. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, Van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, EGG Consortium, Morgen, Camilla S, Van Kampen, Antoine HC, Van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, Van Zuydam, Natalie R, Medina-Gomez, Carolina, De Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, Trier, Caecilie, Van Beijsterveldt, Catharina EM, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, Van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja GM, Vrijheid, Martine, De Geus, Eco JCN, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild IA, Bisgaard, Hans, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent WV, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan FA, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John RB, Evans, David M, and Freathy, Rachel M

Subjects
Adult, Male, Heart Diseases, Models, Genetic, Infant, Newborn, Blood Pressure, Polymorphism, Single Nucleotide, Body Height, 3. Good health, Fetal Development, Diabetes Mellitus, Type 2, Metabolic Diseases, Pregnancy, Risk Factors, Birth Weight, Humans, Female, Genetic Predisposition to Disease, Maternal Inheritance, Maternal-Fetal Exchange, Genome-Wide Association Study
Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

30. Association of Birth Weight With Type 2 Diabetes and Glycemic Traits

Author

Huang, Tao, Wang, Tiange, Zheng, Yan, Ellervik, Christina, Li, Xiang, Gao, Meng, Fang, Zhe, Chai, Jin-Fang, Ahluwalia, Tarun veer S., Wang, Yujie, Voortman, Trudy, Noordam, Raymond, Frazier-Wood, Alexis, Scholz, Markus, Sonestedt, Emily, Akiyama, Masato, Dorajoo, Rajkumar, Zhou, Ang, Kilpeläinen, Tuomas O., Kleber, Marcus E., Crozier, Sarah R., Godfrey, Keith M., Lemaitre, Rozenn, Felix, Janine F., Shi, Yuan, Gupta, Preeti, Khor, Chiea-Chuen, Lehtimäki, Terho, Wang, Carol A., Tiesler, Carla M. T., Thiering, Elisabeth, Standl, Marie, Rzehak, Peter, Marouli, Eirini, He, Meian, Lecoeur, Cécile, Corella, Dolores, Lai, Chao-Qiang, Moreno, Luis A., Pitkänen, Niina, Boreham, Colin A., Zhang, Tao, Saw, Seang Mei, Ridker, Paul M., Graff, Mariaelisa, van Rooij, Frank J. A., Uitterlinden, Andre G., Hofman, Albert, van Heemst, Diana, Rosendaal, Frits R., de Mutsert, Renée, Burkhardt, Ralph, Schulz, Christina-Alexandra, Ericson, Ulrika, Kamatani, Yoichiro, Yuan, Jian-Min, Power, Chris, Hansen, Torben, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Delgado, Graciela, Cooper, Cyrus, Djousse, Luc, Rivadeneira, Fernando, Jameson, Karen, Zhao, Wanting, Liu, Jianjun, Lee, Nanette R., Raitakari, Olli, Kähönen, Mika, Viikari, Jorma, Grote, Veit, Langhendries, Jean-Paul, Koletzko, Berthold, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, Yu, Caizheng, Tham, Yih Chung, Lim, Blanche, Lim, Sing Hui, Froguel, Philippe, Balkau, Beverley, Fink, Nadia R., Vinding, Rebecca K., Sevelsted, Astrid, Bisgaard, Hans, Coltell, Oscar, Dallongeville, Jean, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, Pedersen, Oluf, März, Winfried, Inskip, Hazel, Jaddoe, Vincent W. V., Dennison, Elaine, Wong, Tien Yin, Sabanayagam, Charumathi, Tai, E-Shyong, Mohlke, Karen L., Mackey, David A., Gruszfeld, Dariusz, Deloukas, Panagiotis, Tucker, Katherine L., Fumeron, Frédéric, Bønnelykke, Klaus, Rossing, Peter, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Meirhaeghe, Aline, Amouyel, Philippe, Cheng, Ching-Yu, Sim, Xueling, Teo, Yik Ying, van Dam, Rob M., Koh, Woon-Puay, Orho-Melander, Marju, Loeffler, Markus, Kubo, Michiaki, Thiery, Joachim, Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., Franco, Oscar H., Wu, Tangchun, North, Kari E., Davey Smith, George, Chavarro, Jorge E., Chasman, Daniel I., and Qi, Lu

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31. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Author

Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, Scholz M, van der Most PJ, Monnereau C, Stergiakouli E, Heiskala A, Horikoshi M, Fedko IO, Vilor-Tejedor N, Cousminer DL, Standl M, Wang CA, Viikari J, Geller F, Íñiguez C, Pitkänen N, Chesi A, Bacelis J, Yengo L, Torrent M, Ntalla I, Helgeland Ø, Selzam S, Vonk JM, Zafarmand MH, Heude B, Farooqi IS, Alyass A, Beaumont RN, Have CT, Rzehak P, Bilbao JR, Schnurr TM, Barroso I, Bønnelykke K, Beilin LJ, Carstensen L, Charles MA, Chawes B, Clément K, Closa-Monasterolo R, Custovic A, Eriksson JG, Escribano J, Groen-Blokhuis M, Grote V, Gruszfeld D, Hakonarson H, Hansen T, Hattersley AT, Hollensted M, Hottenga JJ, Hyppönen E, Johansson S, Joro R, Kähönen M, Karhunen V, Kiess W, Knight BA, Koletzko B, Kühnapfel A, Landgraf K, Langhendries JP, Lehtimäki T, Leinonen JT, Li A, Lindi V, Lowry E, Bustamante M, Medina-Gomez C, Melbye M, Michaelsen KF, Morgen CS, Mori TA, Nielsen TRH, Niinikoski H, Oldehinkel AJ, Pahkala K, Panoutsopoulou K, Pedersen O, Pennell CE, Power C, Reijneveld SA, Rivadeneira F, Simpson A, Sly PD, Stokholm J, Teo KK, Thiering E, Timpson NJ, Uitterlinden AG, van Beijsterveldt CEM, van Schaik BDC, Vaudel M, Verduci E, Vinding RK, Vogel M, Zeggini E, Sebert S, Lind MV, Brown CD, Santa-Marina L, Reischl E, Frithioff-Bøjsøe C, Meyre D, Wheeler E, Ong K, Nohr EA, Vrijkotte TGM, Koppelman GH, Plomin R, Njølstad PR, Dedoussis GD, Froguel P, Sørensen TIA, Jacobsson B, Freathy RM, Zemel BS, Raitakari O, Vrijheid M, Feenstra B, Lyytikäinen LP, Snieder H, Kirsten H, Holt PG, Heinrich J, Widén E, Sunyer J, Boomsma DI, Järvelin MR, Körner A, Davey Smith G, Holm JC, Atalay M, Murray C, Bisgaard H, McCarthy MI, Jaddoe VWV, Grant SFA, and Felix JF

Subjects
Adolescent, Adult, Blood Pressure, Body Mass Index, Cardiometabolic Risk Factors, Cardiovascular Diseases pathology, Child, Child, Preschool, Diabetes Mellitus, Type 2 pathology, Female, Genome-Wide Association Study methods, Humans, Male, Menarche genetics, Mendelian Randomization Analysis, Waist-Hip Ratio, Cardiovascular Diseases genetics, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease, Monosaccharide Transport Proteins genetics, Nedd4 Ubiquitin Protein Ligases genetics
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MMcC: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. He serves on advisory panels for Pfizer, NovoNordisk, Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. MS receives funding from Pfizer Inc. for a project not related to this research. IB and spouse own stock in GlaxoSmithKline and Incyte Corp. ZE and CDB currently serve on the editorial board of PLOS Genetics. AC reports personal fees from Novartis, personal fees from Thermo Fisher Scientific, personal fees from Philips, personal fees from Sanofi, personal fees from Stallergenes Greer, outside the submitted work. KC in involved in consultancy for Danone Research, LNC-therapeutic and Confo-therapeutic but no personal funding is received and this activity not linked to the present research.

Published
2020
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32. Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

Author

Huang T, Wang T, Zheng Y, Ellervik C, Li X, Gao M, Fang Z, Chai JF, Ahluwalia TVS, Wang Y, Voortman T, Noordam R, Frazier-Wood A, Scholz M, Sonestedt E, Akiyama M, Dorajoo R, Zhou A, Kilpeläinen TO, Kleber ME, Crozier SR, Godfrey KM, Lemaitre R, Felix JF, Shi Y, Gupta P, Khor CC, Lehtimäki T, Wang CA, Tiesler CMT, Thiering E, Standl M, Rzehak P, Marouli E, He M, Lecoeur C, Corella D, Lai CQ, Moreno LA, Pitkänen N, Boreham CA, Zhang T, Saw SM, Ridker PM, Graff M, van Rooij FJA, Uitterlinden AG, Hofman A, van Heemst D, Rosendaal FR, de Mutsert R, Burkhardt R, Schulz CA, Ericson U, Kamatani Y, Yuan JM, Power C, Hansen T, Sørensen TIA, Tjønneland A, Overvad K, Delgado G, Cooper C, Djousse L, Rivadeneira F, Jameson K, Zhao W, Liu J, Lee NR, Raitakari O, Kähönen M, Viikari J, Grote V, Langhendries JP, Koletzko B, Escribano J, Verduci E, Dedoussis G, Yu C, Tham YC, Lim B, Lim SH, Froguel P, Balkau B, Fink NR, Vinding RK, Sevelsted A, Bisgaard H, Coltell O, Dallongeville J, Gottrand F, Pahkala K, Niinikoski H, Hyppönen E, Pedersen O, März W, Inskip H, Jaddoe VWV, Dennison E, Wong TY, Sabanayagam C, Tai ES, Mohlke KL, Mackey DA, Gruszfeld D, Deloukas P, Tucker KL, Fumeron F, Bønnelykke K, Rossing P, Estruch R, Ordovas JM, Arnett DK, Meirhaeghe A, Amouyel P, Cheng CY, Sim X, Teo YY, van Dam RM, Koh WP, Orho-Melander M, Loeffler M, Kubo M, Thiery J, Mook-Kanamori DO, Mozaffarian D, Psaty BM, Franco OH, Wu T, North KE, Davey Smith G, Chavarro JE, Chasman DI, and Qi L

Subjects
Adolescent, Adult, Aged, Asian People genetics, Blood Glucose metabolism, Diabetes Mellitus, Type 2 genetics, Asia, Eastern, Female, Genetic Variation, Glycated Hemoglobin metabolism, Humans, Infant, Newborn, Insulin metabolism, Male, Mendelian Randomization Analysis, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, White People genetics, Young Adult, Birth Weight genetics, Diabetes Mellitus, Type 2 epidemiology
Abstract

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations., Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis., Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included., Main Outcomes and Measures: Type 2 diabetes and glycemic traits., Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration., Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

Published
2019
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