Author: "Mcmahon, G. (George)" - Searchworks@Jio Institute Digital Library Search Results

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23 results on '"Mcmahon, G. (George)"'

1. Common variation at 16p11.2 is associated with glycosuria in pregnancy:findings from a genome-wide association study in European women

Author: Lee, M. A. (Matthew A.), McMahon, G. (George), Karhunen, V. (Ville), Wade, K. H. (Kaitlin H.), Corbin, L. J. (Laura J.), Hughes, D. A. (David A.), Smith, G. D. (George Davey), Lawlor, D. A. (Debbie A.), Jarvelin, M.-R. (Marjo-Riitta), and Timpson, N. J. (Nicholas J.)
Subjects: endocrine system, genome-wide association study, glycosuria, endocrine system diseases, offspring, genotype, nutritional and metabolic diseases, type 2 [diabetes mellitus], self-report, alspac study, mothers, single nucleotide polymorphism, genetics, pregnancy
Abstract: Glycosuria is a condition where glucose is detected in urine at higher concentrations than normal (i.e. not detectable). Glycosuria at some point during pregnancy has an estimated prevalence of 50% and is associated with adverse outcomes in both mothers and offspring. Little is currently known about the genetic contribution to this trait or the extent to which it overlaps with other seemingly related traits, e.g. diabetes. We performed a genome-wide association study (GWAS) for self-reported glycosuria in pregnant mothers from the Avon Longitudinal Study of Parents and Children (cases/controls = 1249/5140). We identified two loci, one of which (lead SNP = rs13337037; chromosome 16; odds ratio of glycosuria per effect allele: 1.42; 95% CI: 1.30, 1.56; P = 1.97 × 10⁻¹³) was then validated using an obstetric measure of glycosuria measured in the same cohort (227/6639). We performed a secondary GWAS in the 1986 Northern Finland Birth Cohort (NFBC1986; 747/2991) using midwife-reported glycosuria and offspring genotype as a proxy for maternal genotype. The combined results revealed evidence for a consistent effect on glycosuria at the chromosome 16 locus. In follow-up analyses, we saw little evidence of shared genetic underpinnings with the exception of urinary albumin-to-creatinine ratio (Rg = 0.64; SE = 0.22; P = 0.0042), a biomarker of kidney disease. In conclusion, we identified a genetic association with self-reported glycosuria during pregnancy, with the lead SNP located 15kB upstream of SLC5A2, a target of antidiabetic drugs. The lack of strong genetic correlation with seemingly related traits such as type 2 diabetes suggests different genetic risk factors exist for glycosuria during pregnancy.
Published: 2020

2. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
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3. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author: Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), Chasman, D.I. (Daniel), Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), and Chasman, D.I. (Daniel)
Abstract: Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
Published: 2020
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4. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

Author: Meddens, S.F.W. (Fleur), Vlaming, R. (Ronald) de, Bowers, P. (Peter), Burik, C.A.P. (Casper A. P.), Linnér, R.K. (Richard Karlsson), Lee, C. (Chanwook), Okbay, A. (Aysu), Turley, P. (Patrick), Rietveld, C.A. (Cornelius A.), Fontana, M.A. (Mark Alan), Ghanbari, M. (Mohsen), Imamura, F. (Fumiaki), McMahon, G. (George), Most, P.J. (Peter) van der, Voortman, R.G. (Trudy), Wade, K.H. (Kaitlin H.), Anderson, E.L. (Emma L.), Braun, K.V.E. (Kim), Emmett, P.M. (Pauline M.), Esko, T. (Tõnu), Gonzalez, J.R. (Juan), Kiefte-de Jong, J.C. (Jessica), Langenberg, C. (Claudia), Luan, J. (Jian’an), Muka, T. (Taulant), Ring, S.M. (Susan), Rivadeneira, F. (Fernando), Snieder, H. (Harold), Rooij, F.J.A. (Frank) van, Wolffenbuttel, B.H.R. (Bruce), Smith, G.D. (George Davey), Franco, O.H. (Oscar H.), Forouhi, N.G. (Nita), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), van Vliet-Ostaptchouk, J.V. (Jana V.), Wareham, N.J. (Nick), Cesarini, D. (David), Harden, K.P. (K. Paige), Lee, J.J. (James J.), Benjamin, D.J. (Daniel J.), Chow, C.C. (Carson C.), Koellinger, P.D. (Philipp D.), Meddens, S.F.W. (Fleur), Vlaming, R. (Ronald) de, Bowers, P. (Peter), Burik, C.A.P. (Casper A. P.), Linnér, R.K. (Richard Karlsson), Lee, C. (Chanwook), Okbay, A. (Aysu), Turley, P. (Patrick), Rietveld, C.A. (Cornelius A.), Fontana, M.A. (Mark Alan), Ghanbari, M. (Mohsen), Imamura, F. (Fumiaki), McMahon, G. (George), Most, P.J. (Peter) van der, Voortman, R.G. (Trudy), Wade, K.H. (Kaitlin H.), Anderson, E.L. (Emma L.), Braun, K.V.E. (Kim), Emmett, P.M. (Pauline M.), Esko, T. (Tõnu), Gonzalez, J.R. (Juan), Kiefte-de Jong, J.C. (Jessica), Langenberg, C. (Claudia), Luan, J. (Jian’an), Muka, T. (Taulant), Ring, S.M. (Susan), Rivadeneira, F. (Fernando), Snieder, H. (Harold), Rooij, F.J.A. (Frank) van, Wolffenbuttel, B.H.R. (Bruce), Smith, G.D. (George Davey), Franco, O.H. (Oscar H.), Forouhi, N.G. (Nita), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), van Vliet-Ostaptchouk, J.V. (Jana V.), Wareham, N.J. (Nick), Cesarini, D. (David), Harden, K.P. (K. Paige), Lee, J.J. (James J.), Benjamin, D.J. (Daniel J.), Chow, C.C. (Carson C.), and Koellinger, P.D. (Philipp D.)
Abstract: We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.
Published: 2020
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5. Migraine polygenic risk score associates with efficacy of migraine-specific drugs

Author: Kogelman, L. J. (Lisette J. A.), Esserlind, A.-L. (Ann-Louise), Christensen, A. F. (Anne Francke), Awasthi, S. (Swapnil), Ripke, S. (Stephan), Ingason, A. (Andres), Davidsson, O. B. (Olafur B.), Erikstrup, C. (Christian), Hjalgrim, H. (Henrik), Ullum, H. (Henrik), Olesen, J. (Jes), Hansen, T. F. (Thomas Folkmann), Gudbjartsson, D. (Daniel), Gastafsson, O. (Omar), Stefansson, K. (Kari), Stefansson, H. (Hreinn), Porsteinsdottir, U. (Unnur), Andersen, S. (Steffen), Banasik, K. (Karina), Brunak, S. (Soren), Buil, A. (Alfonso), Burgdorf, K. (Kristoffer), Gregor, J. (Jemec), Jennum, P. (Poul), Nielsen, K. R. (Kasper Rene), Nyegaard, M. (Mette), Paarup, H. M. (Helene Mariana), Pedersen, O. B. (Ole Birger), Sorensen, E. (Erik), Werge, T. (Thomas), Anttila, V. (Verneri), Artto, V. (Ville), Belin, A. C. (Andrea Carmine), de Boer, I. (Irene), Boomsma, D. I. (Dorret, I), Borte, S. (Sigrid), Chasman, D. I. (Daniel, I), Cherkas, L. (Lynn), Cormand, B. (Bru), Cuenca-Leon, E. (Ester), Davey-Smith, G. (George), Dichgans, M. (Martin), van Duijn, C. (Cornelia), Esko, T. (Tonu), Ferrari, M. (Michel), Frants, R. R. (Rune R.), Freilinger, T. (Tobias), Furlotte, N. (Nick), Gormley, P. (Padhraig), Griffiths, L. (Lyn), Hamalainen, E. (Eija), Hiekkala, M. (Marjo), Ikram, M. A. (M. Arfan), Järvelin, M.-R. (Marjo-Riitta), Kajanne, R. (Risto), Kallela, M. (Mikko), Kaprio, J. (Jaakko), Kaunisto, M. (Mari), Kubisch, C. (Christian), Kurki, M. (Mitja), Kurth, T. (Tobias), Launer, L. (Lenore), Lehtimaki, T. (Terho), Lessel, D. (Davor), Ligthart, L. (Lannie), Litterman, N. (Nadia), van den Maagdenberg, A. (Arn), Macaya, A. (Alfons), Malik, R. (Rainer), Mangino, M. (Massimo), McMahon, G. (George), Muller-Myhsok, B. (Bertram), Neale, B. M. (Benjamin M.), Northover, C. (Carrie), Nyholt, D. R. (Dale R.), Palotie, A. (Aarno), Palta, P. (Priit), Pedersen, L. (Linda), Pedersen, N. (Nancy), Posthuma, D. (Danielle), Pozo-Rosich, P. (Patricia), Pressman, A. (Alice), Raitakari, O. (Olli), Schurks, M. (Markus), Sintas, C. (Celia), Steinberg, S. (Stacy), Strachan, D. (David), Terwindt, G. (Gisela), Vila-Pueyo, M. (Marta), Wessman, M. (Maija), Winsvold, B. S. (Bendik S.), Zhao, H. (Huiying), Zwart, J.-A. (John-Anker), Kogelman, L. J. (Lisette J. A.), Esserlind, A.-L. (Ann-Louise), Christensen, A. F. (Anne Francke), Awasthi, S. (Swapnil), Ripke, S. (Stephan), Ingason, A. (Andres), Davidsson, O. B. (Olafur B.), Erikstrup, C. (Christian), Hjalgrim, H. (Henrik), Ullum, H. (Henrik), Olesen, J. (Jes), Hansen, T. F. (Thomas Folkmann), Gudbjartsson, D. (Daniel), Gastafsson, O. (Omar), Stefansson, K. (Kari), Stefansson, H. (Hreinn), Porsteinsdottir, U. (Unnur), Andersen, S. (Steffen), Banasik, K. (Karina), Brunak, S. (Soren), Buil, A. (Alfonso), Burgdorf, K. (Kristoffer), Gregor, J. (Jemec), Jennum, P. (Poul), Nielsen, K. R. (Kasper Rene), Nyegaard, M. (Mette), Paarup, H. M. (Helene Mariana), Pedersen, O. B. (Ole Birger), Sorensen, E. (Erik), Werge, T. (Thomas), Anttila, V. (Verneri), Artto, V. (Ville), Belin, A. C. (Andrea Carmine), de Boer, I. (Irene), Boomsma, D. I. (Dorret, I), Borte, S. (Sigrid), Chasman, D. I. (Daniel, I), Cherkas, L. (Lynn), Cormand, B. (Bru), Cuenca-Leon, E. (Ester), Davey-Smith, G. (George), Dichgans, M. (Martin), van Duijn, C. (Cornelia), Esko, T. (Tonu), Ferrari, M. (Michel), Frants, R. R. (Rune R.), Freilinger, T. (Tobias), Furlotte, N. (Nick), Gormley, P. (Padhraig), Griffiths, L. (Lyn), Hamalainen, E. (Eija), Hiekkala, M. (Marjo), Ikram, M. A. (M. Arfan), Järvelin, M.-R. (Marjo-Riitta), Kajanne, R. (Risto), Kallela, M. (Mikko), Kaprio, J. (Jaakko), Kaunisto, M. (Mari), Kubisch, C. (Christian), Kurki, M. (Mitja), Kurth, T. (Tobias), Launer, L. (Lenore), Lehtimaki, T. (Terho), Lessel, D. (Davor), Ligthart, L. (Lannie), Litterman, N. (Nadia), van den Maagdenberg, A. (Arn), Macaya, A. (Alfons), Malik, R. (Rainer), Mangino, M. (Massimo), McMahon, G. (George), Muller-Myhsok, B. (Bertram), Neale, B. M. (Benjamin M.), Northover, C. (Carrie), Nyholt, D. R. (Dale R.), Palotie, A. (Aarno), Palta, P. (Priit), Pedersen, L. (Linda), Pedersen, N. (Nancy), Posthuma, D. (Danielle), Pozo-Rosich, P. (Patricia), Pressman, A. (Alice), Raitakari, O. (Olli), Schurks, M. (Markus), Sintas, C. (Celia), Steinberg, S. (Stacy), Strachan, D. (David), Terwindt, G. (Gisela), Vila-Pueyo, M. (Marta), Wessman, M. (Maija), Winsvold, B. S. (Bendik S.), Zhao, H. (Huiying), and Zwart, J.-A. (John-Anker)
Abstract: Objective: To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response. Methods: We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome. Results: A twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response. Conclusions: The migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.
Published: 2019

6. Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero

Author: Warrington, N.M. (Nicole M.), Shevroja, E. (Enisa), Hemani, G., Hysi, P.G. (Pirro), Jiang, Y. (Yunxuan), Auton, A. (Adam), Boer, C.G. (Cindy), Mangino, M. (Massimo), Wang, C.A. (Carol A.), Kemp, J.P. (John), Mcmahon, G. (George), Medina-Gomez, M.C. (Carolina), Hickey, M. (Martha), Trajanoska, K. (Katerina), Wolke, D. (Dieter), Ikram, M.A. (Arfan), Montgomery, G.W. (Grant W.), Felix, J.F. (Janine F.), Wright, M.J. (Margaret J.), Mackey, D.A. (David), Jaddoe, V.W.V. (Vincent), Martin, N.G. (Nicholas), Tung, J.Y. (Joyce Y.), Smith, G.D. (George Davey), Pennell, C.E. (Craig), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Rivadeneira, F. (Fernando), Medland, S.E. (Sarah), Evans, D.M. (David M.), The 23and Me Research Team, (), Warrington, N.M. (Nicole M.), Shevroja, E. (Enisa), Hemani, G., Hysi, P.G. (Pirro), Jiang, Y. (Yunxuan), Auton, A. (Adam), Boer, C.G. (Cindy), Mangino, M. (Massimo), Wang, C.A. (Carol A.), Kemp, J.P. (John), Mcmahon, G. (George), Medina-Gomez, M.C. (Carolina), Hickey, M. (Martha), Trajanoska, K. (Katerina), Wolke, D. (Dieter), Ikram, M.A. (Arfan), Montgomery, G.W. (Grant W.), Felix, J.F. (Janine F.), Wright, M.J. (Margaret J.), Mackey, D.A. (David), Jaddoe, V.W.V. (Vincent), Martin, N.G. (Nicholas), Tung, J.Y. (Joyce Y.), Smith, G.D. (George Davey), Pennell, C.E. (Craig), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Rivadeneira, F. (Fernando), Medland, S.E. (Sarah), Evans, D.M. (David M.), and The 23and Me Research Team, ()
Abstract: The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sexspecific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N=15 661, with replication N=75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (b=0.06; P=0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population.
Published: 2018
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7. Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study

Author: Richmond, R.C. (Rebecca C.), Timpson, N.J. (Nicholas), Felix, J.F. (Janine), Palmer, T.M. (Tom), Gaillard, R. (Romy), Mcmahon, G. (George), Smith, A.V. (Davey), Jaddoe, V.W.V. (Vincent), Lawlor, D.A. (Debbie A.), Richmond, R.C. (Rebecca C.), Timpson, N.J. (Nicholas), Felix, J.F. (Janine), Palmer, T.M. (Tom), Gaillard, R. (Romy), Mcmahon, G. (George), Smith, A.V. (Davey), Jaddoe, V.W.V. (Vincent), and Lawlor, D.A. (Debbie A.)
Abstract: Background: It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood. Methods and Findings: We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample). In confounder-adjusted multivariable regression in ALSPAC, a 1 standard deviation (SD, equivalent of 3.7 kg/m2) increase in maternal BMI was associated with a 0.25 SD (95% CI 0.21–0.29) increase in offspring BMI at age 7, with similar results at later ages and when FMI was used as the outcome. A weighted genetic risk score was generated from 32 genetic variants robust
Published: 2017
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8. Genome-wide associations for birth weight and correlations with adult disease

Author: Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), Freathy, R.M. (Rachel), Horikoshi, M. (Momoko), Beaumont, R.N. (Robin N.), Day, F.R. (Felix), Warrington, N.M. (Nicole), Kooijman, M.N. (Marjolein), Fernandez-Tajes, J. (Juan), Feenstra, B. (Bjarke), Van Zuydam, N.R. (Natalie R.), Gaulton, K. (Kyle), Grarup, N. (Niels), Bradfield, J.P. (Jonathan), Strachan, D.P. (David), Li-Gao, R. (Ruifang), Ahluwalia, T.S. (Tarunveer Singh), Kreiner, E. (Eskil), Rueedi, R. (Rico), Lyytikäinen, L.-P. (Leo-Pekka), Cousminer, D.L. (Diana), Wu, Y. (Ying), Thiering, E. (Elisabeth), Wang, C.A. (Carol A.), Have, C.T. (Christian T.), Hottenga, J.J. (Jouke Jan), Vilor-Tejedor, N. (Natàlia), Joshi, P.K. (Peter), Boh, E.T.H. (Eileen Tai Hui), Ntalla, I. (Ioanna), Pitkanen, N. (Niina), Mahajan, A. (Anubha), Leeuwen, E.M. (Elisa) van, Joro, R. (Raimo), Lagou, V. (Vasiliki), Nodzenski, M. (Michael), Diver, L.A. (Louise A.), Zondervan, K.T. (Krina), Bustamante, M. (Mariona), Marques-Vidal, P. (Pedro), Mercader, J.M. (Josep), Bennett, A.J. (Amanda), Rahmioglu, N. (Nilufer), Nyholt, D.R. (Dale), Ma, R.C.W. (Ronald C. W.), Tam, C.H.T. (Claudia H. T.), Tam, W.H. (Wing Hung), Ganesh, S.K. (Santhi), Rooij, F.J.A. (Frank) van, Jones, S.E. (Samuel E.), Loh, P.-R. (Po-Ru), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Yaghootkar, H. (Hanieh), Scholtens, D.M. (Denise M.), Paternoster, L. (Lavinia), Prokopenko, I. (Inga), Kovacs, P. (Peter), Atalay, M. (Mustafa), Willems, S.M. (Sara), Panoutsopoulou, K. (Kalliope), Wang, X. (Xu), Carstensen, L. (Lisbeth), Geller, F. (Frank), Schraut, K.E. (Katharina E.), Murcia, M. (Mario), Beijsterveldt, C.E.M. (Toos) van, Willemsen, G.A.H.M. (Gonneke), Appel, E.V.R. (Emil V. R.), Fonvig, C.E. (Cilius E.), Trier, C. (Caecilie), Tiesler, C.M.T. (Carla M. T.), Standl, E. (Eberhard), Kutalik, Z. (Zoltán), Bonàs-Guarch, S. (Silvia), Hougaard, D.M. (David), Sánchez, F. (Friman), Torrents, D. (David), Waage, J. (Johannes), Hollegaard, M.V. (Mads V), Haan, H.G. (Hugoline) de, Rosendaal, F.R. (Frits), Medina-Gomez, C. (Carolina), Ring, S.M. (Susan), Hemani, G., Mcmahon, G. (George), Robertson, N.R. (Neil), Groves, C.J. (Christopher), Langenberg, C. (Claudia), Luan, J. (Jian'An), Scott, R.A. (Robert), Zhao, J.H. (Jing Hua), Mentch, F.D. (Frank), MacKenzie, S.M. (Scott M.), Reynolds, R.M. (Rebecca), Lowe Jr., W.L. (William), Tönjes, A. (Anke), Stumvoll, M. (Michael), Lindi, V. (Virpi), Lakka, T.A. (Timo), Duijn, C.M. (Cornelia) van, Kieß, W. (Wieland), KöRner, A. (Antje), Sørensen, T.I.A. (Thorkild), Niinikoski, H. (Harri), Pahkala, K. (Katja), Raitakari, O.T. (Olli T.), Zeggini, E. (Eleftheria), Dedoussis, G.V. (George), Teo, Y.Y. (Yik Ying), Saw, S.-M. (Seang-Mei), Melbye, M. (Mads), Campbell, H. (Harry), Wilson, J.F. (James F.), Vrijheid, M. (Martine), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Kadarmideen, H.N. (Haja N.), Holm, J.-C. (Jens-Christian), Hansen, T. (T.), Sebert, S. (Sylvain), Hattersley, A.T. (Andrew), Beilin, L.J. (Lawrence), Newnham, J.P. (John), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Adair, L.S. (Linda), Borja, J.B. (Judith), Mohlke, K.L. (Karen), Hagen, K. (Knut), Widen, E. (Elisabeth), Kähönen, M. (Mika), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Vollenweider, P. (Peter), Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Mook-Kanamori, D.O. (Dennis), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Pisinger, C. (Charlotta), Pedersen, O. (Oluf), Power, C. (Christopher), Hypponen, E. (Elina), Wareham, N.J. (Nick), Hakonarson, H. (Hakon), Davies, E. (Eleanor), Walker, B.R. (Brian R.), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Grant, S.F.A. (Struan), Vaag, A.A. (Allan A.), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Smith, A.V. (Davey), Morris, A.P. (Andrew), Ong, K.K. (Ken), Felix, J.F. (Janine), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Evans, D.M. (David), McCarthy, M.I. (Mark), and Freathy, R.M. (Rachel)
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg =-0.22, P = 5.5 × 10-13), T2D (Rg =-0.27, P = 1.1 × 10-6) and coronary artery disease (Rg =-0.30, P = 6.5 × 10-9). In addition, using large-cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.
Published: 2016
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9. Genome-wide association study identifies 74 loci associated with educational attainment

Author: Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Benjamin, D.J. (Daniel J.), Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), and Benjamin, D.J. (Daniel J.)
Abstract: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016
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10. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), and Palotie, A. (Aarno)
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10-8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016
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11. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016
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12. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author: Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
Published: 2016
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13. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Author: Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), Kelly, A. (Andrea), Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), and Kelly, A. (Andrea)
Abstract: A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10-8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in streng
Published: 2016
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14. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight

Author: Tyrrell, J. (Jessica), Richmond, R. C. (Rebecca C.), Palmer, T. M. (Tom M.), Feenstra, B. (Bjarke), Rangarajan, J. (Janani), Metrustry, S. (Sarah), Cavadino, A. (Alana), Paternoster, L. (Lavinia), Armstrong, L. L. (Loren L.), De Silva, N. M. (N. Maneka G.), Wood, A. R. (Andrew R.), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Bradfield, J. P. (Jonathan P.), Kreiner-Moller, E. (Eskil), Huikari, V. (Ville), Painter, J. N. (Jodie N.), Hottenga, J.-J. (Jouke-Jan), Allard, C. (Catherine), Berry, D. J. (Diane J.), Bouchard, L. (Luigi), Das, S. (Shikta), Evans, D. M. (David M.), Hakonarson, H. (Hakon), Hayes, M. G. (M. Geoffrey), Heikkinen, J. (Jani), Hofman, A. (Albert), Knight, B. (Bridget), Lind, P. A. (Penelope A.), McCarthy, M. I. (Mark I.), McMahon, G. (George), Medland, S. E. (Sarah E.), Melbye, M. (Mads), Morris, A. P. (Andrew P.), Nodzenski, M. (Michael), Reichetzeder, C. (Christoph), Ring, S. M. (Susan M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Sorensen, T. I. (Thorkild I. A.), Willemsen, G. (Gonneke), de Geus, E. J. (Eco J. C.), Martin, N. G. (Nicholas G.), Spector, T. D. (Tim D.), Power, C. (Christine), Järvelin, M.-R. (Marjo-Riitta), Bisgaard, H. (Hans), Grant, S. F. (Struan F. A.), Nohr, E. A. (Ellen A.), Jaddoe, V. W. (Vincent W.), Jacobsson, B. (Bo), Murray, J. C. (Jeffrey C.), Hocher, B. (Berthold), Hattersley, A. T. (Andrew T.), Scholtens, D. M. (Denise M.), Smith, G. D. (George Davey), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Hypponen, E. (Elina), Lowe, W. L. (William L., Jr.), Frayling, T. M. (Timothy M.), Lawlor, D. A. (Debbie A.), Freathy, R. M. (Rachel M.), Tyrrell, J. (Jessica), Richmond, R. C. (Rebecca C.), Palmer, T. M. (Tom M.), Feenstra, B. (Bjarke), Rangarajan, J. (Janani), Metrustry, S. (Sarah), Cavadino, A. (Alana), Paternoster, L. (Lavinia), Armstrong, L. L. (Loren L.), De Silva, N. M. (N. Maneka G.), Wood, A. R. (Andrew R.), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Bradfield, J. P. (Jonathan P.), Kreiner-Moller, E. (Eskil), Huikari, V. (Ville), Painter, J. N. (Jodie N.), Hottenga, J.-J. (Jouke-Jan), Allard, C. (Catherine), Berry, D. J. (Diane J.), Bouchard, L. (Luigi), Das, S. (Shikta), Evans, D. M. (David M.), Hakonarson, H. (Hakon), Hayes, M. G. (M. Geoffrey), Heikkinen, J. (Jani), Hofman, A. (Albert), Knight, B. (Bridget), Lind, P. A. (Penelope A.), McCarthy, M. I. (Mark I.), McMahon, G. (George), Medland, S. E. (Sarah E.), Melbye, M. (Mads), Morris, A. P. (Andrew P.), Nodzenski, M. (Michael), Reichetzeder, C. (Christoph), Ring, S. M. (Susan M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Sorensen, T. I. (Thorkild I. A.), Willemsen, G. (Gonneke), de Geus, E. J. (Eco J. C.), Martin, N. G. (Nicholas G.), Spector, T. D. (Tim D.), Power, C. (Christine), Järvelin, M.-R. (Marjo-Riitta), Bisgaard, H. (Hans), Grant, S. F. (Struan F. A.), Nohr, E. A. (Ellen A.), Jaddoe, V. W. (Vincent W.), Jacobsson, B. (Bo), Murray, J. C. (Jeffrey C.), Hocher, B. (Berthold), Hattersley, A. T. (Andrew T.), Scholtens, D. M. (Denise M.), Smith, G. D. (George Davey), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Hypponen, E. (Elina), Lowe, W. L. (William L., Jr.), Frayling, T. M. (Timothy M.), Lawlor, D. A. (Debbie A.), and Freathy, R. M. (Rachel M.)
Abstract: Importance: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. Objective: To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Design, Setting, and Participants: Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30 487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Exposures: Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Main Outcome and Measure: Offspring birth weight from 18 studies. Results: Among the 30 487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10−14) and −4 g (95% CI, −6 to −2g) per SBP-raising allele (P = 1×10−5), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 1
Published: 2016

15. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

Author: Li, Q. (Qing), Wojciechowski, R. (Robert), Simpson, C.L. (Claire), Hysi, P.G. (Pirro), Verhoeven, V.J.M. (Virginie), Ikram, M.K. (Kamran), Höhn, R. (René), Vitart, V. (Veronique), Hewit, A.W. (Alex), Oexle, K. (Konrad), Makela, K.M. (Kari Matti), MacGregor, S. (Stuart), Pirastu, M. (Mario), Fan, Q. (Qiao), Cheng, C-Y. (Ching-Yu), St Pourcain, B. (Beate), Mcmahon, G. (George), Kemp, J.P. (John), Northstone, K. (Kate), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Martin, N.G. (Nicholas), Sanfilippo, P.G. (Paul G.), Lu, Y. (Yi), Wang, Y. (Ying), Hayward, C. (Caroline), Polasek, O. (Ozren), Campbell, H. (Harry), Bencic, G. (Goran), Wright, A. (Alan), Wedenoja, J. (Juho), Zeller, T. (Tanja), Schillert, A. (Arne), Mirshahi, A. (Alireza), Lackner, K.J. (Karl), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K. H.), Ried, J.S. (Janina), Gieger, C. (Christian), Murgia, D. (Daniela), Wilson, J.F. (James F), Fleck, B.W. (Brian W.), Yazar, S. (Seyhan), Vingerling, J.R. (Hans), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Oostra, B.A. (Ben), Zhou, X. (Xin), Teo, Y.Y. (Yik Ying), Tai, E.S. (Shyong), Vithana, E.N. (Eranga), Barathi, V.A. (Veluchamy), Zheng, Y. (Yingfeng), Siantar, R. (Rosalynn), Neelam, K. (Kumari), Shin, Y. (Youchan), Lam, J. (Janice), Yonova-Doing, E. (Ekaterina), Venturini, C. (Cristina), Hosseini, S.M. (S Mohsen), Wong, H.-S. (Hoi-Suen), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Raitakari, O. (Olli), Timpson, N.J. (Nicholas), Evans, D.M. (David M.), Khor, C.C., Aung, T. (Tin), Young, T.L. (Terri), Mitchell, P. (Paul), Klein, B.E.K. (Barbara), Duijn, C.M. (Cornelia) van, Meitinger, T. (Thomas), Jonas, J.B. (Jost B.), Baird, P.N. (Paul), Mackey, D.A. (David), Wong, T.Y. (Tien Yin), Saw, S-M. (Seang-Mei), Pärssinen, O. (Olavi), Stambolian, D.E. (Dwight), Hammond, C.J. (Christopher), Klaver, C.C.W. (Caroline), Williams, C. (Cathy), Paterson, A.D. (Andrew), Bailey-Wilson, J.E. (Joan E.), Guggenheim, J. (Jean), Li, Q. (Qing), Wojciechowski, R. (Robert), Simpson, C.L. (Claire), Hysi, P.G. (Pirro), Verhoeven, V.J.M. (Virginie), Ikram, M.K. (Kamran), Höhn, R. (René), Vitart, V. (Veronique), Hewit, A.W. (Alex), Oexle, K. (Konrad), Makela, K.M. (Kari Matti), MacGregor, S. (Stuart), Pirastu, M. (Mario), Fan, Q. (Qiao), Cheng, C-Y. (Ching-Yu), St Pourcain, B. (Beate), Mcmahon, G. (George), Kemp, J.P. (John), Northstone, K. (Kate), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Martin, N.G. (Nicholas), Sanfilippo, P.G. (Paul G.), Lu, Y. (Yi), Wang, Y. (Ying), Hayward, C. (Caroline), Polasek, O. (Ozren), Campbell, H. (Harry), Bencic, G. (Goran), Wright, A. (Alan), Wedenoja, J. (Juho), Zeller, T. (Tanja), Schillert, A. (Arne), Mirshahi, A. (Alireza), Lackner, K.J. (Karl), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K. H.), Ried, J.S. (Janina), Gieger, C. (Christian), Murgia, D. (Daniela), Wilson, J.F. (James F), Fleck, B.W. (Brian W.), Yazar, S. (Seyhan), Vingerling, J.R. (Hans), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Oostra, B.A. (Ben), Zhou, X. (Xin), Teo, Y.Y. (Yik Ying), Tai, E.S. (Shyong), Vithana, E.N. (Eranga), Barathi, V.A. (Veluchamy), Zheng, Y. (Yingfeng), Siantar, R. (Rosalynn), Neelam, K. (Kumari), Shin, Y. (Youchan), Lam, J. (Janice), Yonova-Doing, E. (Ekaterina), Venturini, C. (Cristina), Hosseini, S.M. (S Mohsen), Wong, H.-S. (Hoi-Suen), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Raitakari, O. (Olli), Timpson, N.J. (Nicholas), Evans, D.M. (David M.), Khor, C.C., Aung, T. (Tin), Young, T.L. (Terri), Mitchell, P. (Paul), Klein, B.E.K. (Barbara), Duijn, C.M. (Cornelia) van, Meitinger, T. (Thomas), Jonas, J.B. (Jost B.), Baird, P.N. (Paul), Mackey, D.A. (David), Wong, T.Y. (Tien Yin), Saw, S-M. (Seang-Mei), Pärssinen, O. (Olavi), Stambolian, D.E. (Dwight), Hammond, C.J. (Christopher), Klaver, C.C.W. (Caroline), Williams, C. (Cathy), Paterson, A.D. (Andrew), Bailey-Wilson, J.E. (Joan E.), and Guggenheim, J. (Jean)
Abstract: To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical
Published: 2015
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16. Genetic variation associated with differential educational attainment in adults has anticipated associations with school performance in children

Author: Ward, M.E. (Mary), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Rietveld, C.A. (Niels), Benjamin, D.J. (Daniel J.), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Smith, G.D. (George Davey), Timpson, N.J. (Nicholas), Ward, M.E. (Mary), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Rietveld, C.A. (Niels), Benjamin, D.J. (Daniel J.), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Smith, G.D. (George Davey), and Timpson, N.J. (Nicholas)
Abstract: Genome-wide association study results have yielded evidence for the association of common genetic variants with crude measures of completed educational attainment in adults. Whilst informative, these results do not inform as to the mechanism of these effects or their presence at earlier ages and where educational performance is more routinely and more precisely assessed. Single nucleotide polymorphisms exhibiting genome-wide significant associations with adult educational attainment were combined to derive an unweighted allele score in 5,979 and 6,145 young participants from the Avon Longitudinal Study of Parents and Children with key stage 3 national curriculum test results (SATS results) available at age 13 to 14 years in English and mathematics respectively. Standardised (z-scored) results for English and mathematics showed an expected relationship with sex, with girls exhibiting an advantage over boys in English (0.433 SD (95%CI 0.395, 0.470), p<10-10) with more similar results (though in the opposite direction) in mathematics (0.042 SD (95%CI 0.004, 0.080), p = 0.030). Each additional adult educational attainment increasing allele was associated with 0.041 SD (95%CI 0.020, 0.063), p = 1.79×10-04 and 0.028 SD (95%CI 0.007, 0.050), p = 0.01 increases in standardised SATS score for English and mathematics respectively. Educational attainment is a complex multifactorial behavioural trait which has not had heritable contributions to it fully characterised. We were able to apply the results from a large study of adult educational attainment to a study of child exam performance marking events in the process of learning rather than realised adult end product. Our results support evidence for common, small genetic contributions to educational attainment, but also emphasise the likely lifecourse nature of this genetic effect. Results here also, by an alternative route, suggest that existing methods for child examination are able to recognise early life variation likely t
Published: 2014
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17. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author: Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken K.), Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), and Ong, K.K. (Ken K.)
Abstract: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10-8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarc
Published: 2014
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18. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author: Rietveld, C.A. (Niels), Esko, T. (Tõnu), Davies, G. (Gail), Pers, T.H. (Tune), Turley, P. (Patrick), Benyamin, B. (Beben), Chabris, C.F. (Christopher F.), Emilsson, V. (Valur), Johnson, A.D. (Andrew), Lee, J.J. (James J.), Leeuw, C. (Christiaan) de, Marioni, R.E. (Riccardo), Medland, S.E. (Sarah), Miller, M. (Mike), Rostapshova, O. (Olga), Lee, S.J. (Sven) van der, Vinkhuyzen, A.A.E. (Anna A.), Amin, N. (Najaf), Conley, D. (Dalton), Derringer, J., Duijn, C.M. (Cornelia) van, Fehrmann, R.S.N. (Rudolf), Franke, L. (Lude), Glaeser, E.L. (Edward L.), Hansell, N.K. (Narelle), Hayward, C. (Caroline), Iacono, W.G. (William), Ibrahim-Verbaas, C.A. (Carla), Jaddoe, V.W.V. (Vincent), Karjalainen, J. (Juha), Laibson, D. (David), Lichtenstein, P. (Paul), Liewald, D.C.M. (David), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Mcmahon, G. (George), Pedersen, N.L. (Nancy), Pinker, S. (Steven), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Rivadeneira Ramirez, F. (Fernando), Smithk, B.H. (Blair H.), Starr, J.M. (John), Tiemeier, H.W. (Henning), Timpsonm, N.J. (Nicholas J.), Trzaskowskin, M. (Maciej), Uitterlinden, A.G. (André), Verhulst, F.C. (Frank), Ward, M.E. (Mary), Wright, M.J. (Margaret), Smith, A.V. (Davey), Deary, I.J. (Ian), Johannesson, M. (Magnus), Plomin, R. (Robert), Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Esko, T. (Tõnu), Davies, G. (Gail), Pers, T.H. (Tune), Turley, P. (Patrick), Benyamin, B. (Beben), Chabris, C.F. (Christopher F.), Emilsson, V. (Valur), Johnson, A.D. (Andrew), Lee, J.J. (James J.), Leeuw, C. (Christiaan) de, Marioni, R.E. (Riccardo), Medland, S.E. (Sarah), Miller, M. (Mike), Rostapshova, O. (Olga), Lee, S.J. (Sven) van der, Vinkhuyzen, A.A.E. (Anna A.), Amin, N. (Najaf), Conley, D. (Dalton), Derringer, J., Duijn, C.M. (Cornelia) van, Fehrmann, R.S.N. (Rudolf), Franke, L. (Lude), Glaeser, E.L. (Edward L.), Hansell, N.K. (Narelle), Hayward, C. (Caroline), Iacono, W.G. (William), Ibrahim-Verbaas, C.A. (Carla), Jaddoe, V.W.V. (Vincent), Karjalainen, J. (Juha), Laibson, D. (David), Lichtenstein, P. (Paul), Liewald, D.C.M. (David), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Mcmahon, G. (George), Pedersen, N.L. (Nancy), Pinker, S. (Steven), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Rivadeneira Ramirez, F. (Fernando), Smithk, B.H. (Blair H.), Starr, J.M. (John), Tiemeier, H.W. (Henning), Timpsonm, N.J. (Nicholas J.), Trzaskowskin, M. (Maciej), Uitterlinden, A.G. (André), Verhulst, F.C. (Frank), Ward, M.E. (Mary), Wright, M.J. (Margaret), Smith, A.V. (Davey), Deary, I.J. (Ian), Johannesson, M. (Magnus), Plomin, R. (Robert), Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)
Abstract: We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.
Published: 2014
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19. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment

Author: Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)
Published: 2013
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20. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Author: Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Fan, Q. (Qiao), Guggenheim, J. (Jean), Höhn, R. (René), MacGregor, S. (Stuart), Hewit, A.W. (Alex), Nag, A. (Abhishek), Cheng, C-Y. (Ching-Yu), Yonova-Doing, E. (Ekaterina), Zhou, X. (Xin), Ikram, M.K. (Kamran), Buitendijk, G.H.S. (Gabrielle), Mcmahon, G. (George), Kemp, J.P. (John), Pourcain, B.S. (Beate), Simpson, C.L. (Claire), Mäkelä, M.J., Lehtimäki, T. (Terho), Kähönen, M. (Mika), Paterson, A.D. (Andrew), Hosseini, M. (Mehran), Wong, H.S. (Hoi Suen), Xu, L. (Liang), Jonas, J.B., Pärssinen, O. (Olavi), Wedenoja, J. (Juho), Yip, S.P. (Shea Ping), Ho, D.W.H. (Daniel), Pang, C.P. (Chi), Chen, L.J. (Li), Burdon, K.P. (Kathryn), Craig, J.E. (Jamie), Klein, B.E.K. (Barbara), Haller, T. (Toomas), Metspalu, A. (Andres), Khor, C.C., Tai, E.S. (Shyong), Aung, T. (Tin), Vithana, E.N. (Eranga), Tay, W.-T. (Wan-Ting), Barathi, V.A. (Veluchamy), Chen, P. (Ping), Li, R. (Rui), Liao, J. (Jie), Zheng, Y. (Yuhui), Ong, R.T.H. (Rick Twee-Hee), Döring, A. (Angela), Evans, D.M. (David), Timpson, N.J. (Nicholas), Verkerk, A., Meitinger, T. (Thomas), Raitakari, O. (Olli), Hawthorne, F. (Felicia), Spector, T.D. (Timothy), Karssen, L.C. (Lennart), Pirastu, M. (Mario), Murgia, D. (Daniela), Ang, W.Q. (Wei), Mishra, A. (Aniket), Montgomery, G.W. (Grant), Pennell, C.E. (Craig), Cumberland, P. (Phillippa), Cotlarciuc, I. (Ioana), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Schache, M. (Maria), Janmahasathian, S. (Sarayut), Igo Jr., R.P. (Robert), Lass Jr., J.H. (Jonathan), Chew, E.Y. (Emily), Iyengar, S.K. (Sudha), Gorgels, T.G.M.F. (Theo), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Vatavuk, Z. (Zoran), Wilson, J.F. (James), Fleck, B. (Brian), Zeller, T. (Tanja), Mirshahi, A. (Alireza), Müller, C. (Christian), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Hofman, A. (Albert), Oostra, B.A. (Ben), Amin, N. (Najaf), Bergen, A.A.B. (Arthur), Teo, Y.Y. (Yik Ying), Rahi, J.S. (Jugnoo), Vitart, V. (Veronique), Williams, C. (Cathy), Baird, P.N. (Paul), Wong, T.Y. (Tien Yin), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Young, T.L. (Terri), Duijn, C.M. (Cornelia) van, Saw, S-M. (Seang-Mei), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Klaver, C.C.W. (Caroline), Hammond, C.J. (Christopher), Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Fan, Q. (Qiao), Guggenheim, J. (Jean), Höhn, R. (René), MacGregor, S. (Stuart), Hewit, A.W. (Alex), Nag, A. (Abhishek), Cheng, C-Y. (Ching-Yu), Yonova-Doing, E. (Ekaterina), Zhou, X. (Xin), Ikram, M.K. (Kamran), Buitendijk, G.H.S. (Gabrielle), Mcmahon, G. (George), Kemp, J.P. (John), Pourcain, B.S. (Beate), Simpson, C.L. (Claire), Mäkelä, M.J., Lehtimäki, T. (Terho), Kähönen, M. (Mika), Paterson, A.D. (Andrew), Hosseini, M. (Mehran), Wong, H.S. (Hoi Suen), Xu, L. (Liang), Jonas, J.B., Pärssinen, O. (Olavi), Wedenoja, J. (Juho), Yip, S.P. (Shea Ping), Ho, D.W.H. (Daniel), Pang, C.P. (Chi), Chen, L.J. (Li), Burdon, K.P. (Kathryn), Craig, J.E. (Jamie), Klein, B.E.K. (Barbara), Haller, T. (Toomas), Metspalu, A. (Andres), Khor, C.C., Tai, E.S. (Shyong), Aung, T. (Tin), Vithana, E.N. (Eranga), Tay, W.-T. (Wan-Ting), Barathi, V.A. (Veluchamy), Chen, P. (Ping), Li, R. (Rui), Liao, J. (Jie), Zheng, Y. (Yuhui), Ong, R.T.H. (Rick Twee-Hee), Döring, A. (Angela), Evans, D.M. (David), Timpson, N.J. (Nicholas), Verkerk, A., Meitinger, T. (Thomas), Raitakari, O. (Olli), Hawthorne, F. (Felicia), Spector, T.D. (Timothy), Karssen, L.C. (Lennart), Pirastu, M. (Mario), Murgia, D. (Daniela), Ang, W.Q. (Wei), Mishra, A. (Aniket), Montgomery, G.W. (Grant), Pennell, C.E. (Craig), Cumberland, P. (Phillippa), Cotlarciuc, I. (Ioana), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Schache, M. (Maria), Janmahasathian, S. (Sarayut), Igo Jr., R.P. (Robert), Lass Jr., J.H. (Jonathan), Chew, E.Y. (Emily), Iyengar, S.K. (Sudha), Gorgels, T.G.M.F. (Theo), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Vatavuk, Z. (Zoran), Wilson, J.F. (James), Fleck, B. (Brian), Zeller, T. (Tanja), Mirshahi, A. (Alireza), Müller, C. (Christian), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Hofman, A. (Albert), Oostra, B.A. (Ben), Amin, N. (Najaf), Bergen, A.A.B. (Arthur), Teo, Y.Y. (Yik Ying), Rahi, J.S. (Jugnoo), Vitart, V. (Veronique), Williams, C. (Cathy), Baird, P.N. (Paul), Wong, T.Y. (Tien Yin), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Young, T.L. (Terri), Duijn, C.M. (Cornelia) van, Saw, S-M. (Seang-Mei), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Klaver, C.C.W. (Caroline), and Hammond, C.J. (Christopher)
Abstract: Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.
Published: 2013
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21. Mining the Human Phenome Using Allelic Scores That Index Biological Intermediates

Author: Evans, D.M. (David), Brion, M.-J. (Maria), Paternoster, L. (Lavinia), Kemp, J.P. (John), Mcmahon, G. (George), Munafò, M.R. (Marcus), Whitfield, J. (John), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Timpson, N.J. (Nicholas), St Pourcain, B. (Beate), Lawlor, D.A. (Debbie), Martin, N.G. (Nicholas), Dehghan, A. (Abbas), Hirschhorn, J.N. (Joel), Davey-Smith, G. (George), Evans, D.M. (David), Brion, M.-J. (Maria), Paternoster, L. (Lavinia), Kemp, J.P. (John), Mcmahon, G. (George), Munafò, M.R. (Marcus), Whitfield, J. (John), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Timpson, N.J. (Nicholas), St Pourcain, B. (Beate), Lawlor, D.A. (Debbie), Martin, N.G. (Nicholas), Dehghan, A. (Abbas), Hirschhorn, J.N. (Joel), and Davey-Smith, G. (George)
Abstract: It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: bo
Published: 2013
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22. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Author: Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Saw, S-M. (Seang-Mei), Vitart, V. (Veronique), Mirshahi, A. (Alireza), Guggenheim, J. (Jean), Cotch, M.F. (Mary Frances), Yamashiro, K. (Kenji), Baird, P.N. (Paul), Mackey, D.A. (David), Wojciechowski, R. (Robert), Ikram, M.K. (Kamran), Hewit, A.W. (Alex), Duggal, P. (Priya), Janmahasatian, S. (Sarayut), Khor, C.C., Fan, Q. (Qiao), Zhou, X. (Xinying), Young, T.L. (Terri), Tai, E.S. (Shyong), Goh, L.-K., Li, Y.J. (Yi), Aung, T. (Tin), Vithana, E.N. (Eranga), Teo, Y.Y. (Yik Ying), Tay, W.-T., Sim, X. (Xueling), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Campbell, H. (Harry), Wilson, J.F. (James), Fleck, B. (Brian), Nakata, I. (Isao), Yoshimura, N., Yamada, R. (Ryo), Matsuda, F. (Fumihiko), Ohno-Matsui, K. (Kyoko), Nag, A. (Abhishek), Mcmahon, G. (George), St Pourcain, B. (Beate), Lu, Y. (Yi), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Bhattacharya, S. (Shoumo), Simpson, C.L. (Claire), Atwood, L.D. (Larry), Li, X. (Xiaohui), Raffel, L.J. (Leslie), Murgia, D. (Daniela), Portas, L. (Laura), Despriet, D.D.G. (Dominique), Koolwijk, L.M.E. (Leonieke) van, Wolfram, C. (Christian), Lackner, K.J. (Karl), Tönjes, A. (Anke), Mägi, R. (Reedik), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Esko, T. (Tõnu), Metspalu, A. (Andres), Rantanen, T. (Taina), Pärssinen, O. (Olavi), Klein, B.E.K. (Barbara), Meitinger, T. (Thomas), Spector, T.D. (Timothy), Oostra, B.A. (Ben), Smith, A.V. (Davey), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Amin, N. (Najaf), Karssen, L.C. (Lennart), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Döring, A. (Angela), Bettecken, T. (Thomas), Uitterlinden, A.G. (André), Williams, C. (Cathy), Zeller, T. (Tanja), Castagne, R. (Raphaële), Oexle, K. (Konrad), Duijn, C.M. (Cornelia) van, Iyengar, S.K. (Sudha), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Höhn, R. (René), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Wong, T.Y. (Tien Yin), Hammond, C.J. (Christopher), Klaver, C.C.W. (Caroline), Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Saw, S-M. (Seang-Mei), Vitart, V. (Veronique), Mirshahi, A. (Alireza), Guggenheim, J. (Jean), Cotch, M.F. (Mary Frances), Yamashiro, K. (Kenji), Baird, P.N. (Paul), Mackey, D.A. (David), Wojciechowski, R. (Robert), Ikram, M.K. (Kamran), Hewit, A.W. (Alex), Duggal, P. (Priya), Janmahasatian, S. (Sarayut), Khor, C.C., Fan, Q. (Qiao), Zhou, X. (Xinying), Young, T.L. (Terri), Tai, E.S. (Shyong), Goh, L.-K., Li, Y.J. (Yi), Aung, T. (Tin), Vithana, E.N. (Eranga), Teo, Y.Y. (Yik Ying), Tay, W.-T., Sim, X. (Xueling), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Campbell, H. (Harry), Wilson, J.F. (James), Fleck, B. (Brian), Nakata, I. (Isao), Yoshimura, N., Yamada, R. (Ryo), Matsuda, F. (Fumihiko), Ohno-Matsui, K. (Kyoko), Nag, A. (Abhishek), Mcmahon, G. (George), St Pourcain, B. (Beate), Lu, Y. (Yi), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Bhattacharya, S. (Shoumo), Simpson, C.L. (Claire), Atwood, L.D. (Larry), Li, X. (Xiaohui), Raffel, L.J. (Leslie), Murgia, D. (Daniela), Portas, L. (Laura), Despriet, D.D.G. (Dominique), Koolwijk, L.M.E. (Leonieke) van, Wolfram, C. (Christian), Lackner, K.J. (Karl), Tönjes, A. (Anke), Mägi, R. (Reedik), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Esko, T. (Tõnu), Metspalu, A. (Andres), Rantanen, T. (Taina), Pärssinen, O. (Olavi), Klein, B.E.K. (Barbara), Meitinger, T. (Thomas), Spector, T.D. (Timothy), Oostra, B.A. (Ben), Smith, A.V. (Davey), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Amin, N. (Najaf), Karssen, L.C. (Lennart), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Eiriksdottir, G. (Gudny), Gudnason, V. (Vilmundur), Döring, A. (Angela), Bettecken, T. (Thomas), Uitterlinden, A.G. (André), Williams, C. (Cathy), Zeller, T. (Tanja), Castagne, R. (Raphaële), Oexle, K. (Konrad), Duijn, C.M. (Cornelia) van, Iyengar, S.K. (Sudha), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Höhn, R. (René), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Wong, T.Y. (Tien Yin), Hammond, C.J. (Christopher), and Klaver, C.C.W. (Caroline)
Abstract: Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10 -12 for SNP rs634990 in Caucasians, and 9.65 × 10 -4 for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10 -23 for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10 -2 for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
Published: 2012
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23. Common variants at 12q15 and 12q24 are associated with infant head circumference

Author: Taal, H.R. (Rob), St Pourcain, B. (Beate), Thiering, E. (Eelisabeth), Das, S. (Shikta), Mook-Kanamori, D.O. (Dennis), Warrington, N.M. (Nicole), Kaakinen, M. (Marika), Kreiner-Møller, E. (Eskil), Bradfield, J.P. (Jonathan), Freathy, R.M. (Rachel), Geller, F. (Frank), Guxens Junyent, M. (Mònica), Cousminer, D.L. (Diana), Kerkhof, M. (Marjan), Timpson, N.J. (Nicholas), Ikram, M.A. (Arfan), Beilin, L.J. (Lawrence), Bønnelykke, K. (Klaus), Buxton, J.L. (Jessica), Charoen, P. (Pimphen), Chawes, B.L.K. (Bo Lund Krogsgaard), Eriksson, J.G. (Johan), Evans, D.M. (David), Hofman, A. (Albert), Kemp, J.P. (John), Kim, C.E. (Cecilia), Klopp, N. (Norman), Lahti, J. (Jari), Lye, S.J. (Stephen), Mcmahon, G. (George), Mentch, F.D. (Frank), Müller-Nurasyid, M. (Martina), O'Reilly, P.F. (Paul), Prokopenko, I. (Inga), Rivadeneira Ramirez, F. (Fernando), Steegers, E.A.P. (Eric), Sunyer, J. (Jordi), Tiesler, C. (Carla), Yaghootkar, H. (Hanieh), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), Fornage, M. (Myriam), Gudnason, V. (Vilmunder), Launer, L.J. (Lenore), Lugt, A. (Aad) van der, Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Smith, A.V. (Albert V.), Vernooij, M.W. (Meike), Blakemore, A.I.F. (Alexandra), Chiavacci, R.M. (Rosetta), Feenstra, B. (Bjarke), Fernandez-Banet, J. (Julio), Grant, S.F.A. (Struan), Hartikainen, A.-L. (Anna-Liisa), Heijden, A.J. (Albert) van der, Iniguez, C. (Carmen), Lathrop, M. (Mark), McArdle, W.L. (Wendy), Mølgaard, A. (Anne), Newnham, J.P. (John), Palmer, L.J. (Lyle), Palotie, A. (Aarno), Pouta, A. (Anneli), Ring, S.M. (Susan), Sovio, U. (Ulla), Standl, M. (Marie), Uitterlinden, A.G. (André), Wichmann, E.H. (Erich), Vissing, N.H. (Nadja), DeCarli, C. (Charles), Duijn, C.M. (Cornelia) van, McCarthy, M.I. (M.), Koppelman, G.H. (Gerard), Estivill, X. (Xavier), Hattersley, A.T. (Andrew), Melbye, M. (Mads), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Davey-Smith, G. (George), Heinrich, J. (Joachim), Jarvelin, M.-R. (Marjo-Riitta), Jaddoe, V.W.V. (Vincent), Taal, H.R. (Rob), St Pourcain, B. (Beate), Thiering, E. (Eelisabeth), Das, S. (Shikta), Mook-Kanamori, D.O. (Dennis), Warrington, N.M. (Nicole), Kaakinen, M. (Marika), Kreiner-Møller, E. (Eskil), Bradfield, J.P. (Jonathan), Freathy, R.M. (Rachel), Geller, F. (Frank), Guxens Junyent, M. (Mònica), Cousminer, D.L. (Diana), Kerkhof, M. (Marjan), Timpson, N.J. (Nicholas), Ikram, M.A. (Arfan), Beilin, L.J. (Lawrence), Bønnelykke, K. (Klaus), Buxton, J.L. (Jessica), Charoen, P. (Pimphen), Chawes, B.L.K. (Bo Lund Krogsgaard), Eriksson, J.G. (Johan), Evans, D.M. (David), Hofman, A. (Albert), Kemp, J.P. (John), Kim, C.E. (Cecilia), Klopp, N. (Norman), Lahti, J. (Jari), Lye, S.J. (Stephen), Mcmahon, G. (George), Mentch, F.D. (Frank), Müller-Nurasyid, M. (Martina), O'Reilly, P.F. (Paul), Prokopenko, I. (Inga), Rivadeneira Ramirez, F. (Fernando), Steegers, E.A.P. (Eric), Sunyer, J. (Jordi), Tiesler, C. (Carla), Yaghootkar, H. (Hanieh), Breteler, M.M.B. (Monique), Debette, S. (Stéphanie), Fornage, M. (Myriam), Gudnason, V. (Vilmunder), Launer, L.J. (Lenore), Lugt, A. (Aad) van der, Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Smith, A.V. (Albert V.), Vernooij, M.W. (Meike), Blakemore, A.I.F. (Alexandra), Chiavacci, R.M. (Rosetta), Feenstra, B. (Bjarke), Fernandez-Banet, J. (Julio), Grant, S.F.A. (Struan), Hartikainen, A.-L. (Anna-Liisa), Heijden, A.J. (Albert) van der, Iniguez, C. (Carmen), Lathrop, M. (Mark), McArdle, W.L. (Wendy), Mølgaard, A. (Anne), Newnham, J.P. (John), Palmer, L.J. (Lyle), Palotie, A. (Aarno), Pouta, A. (Anneli), Ring, S.M. (Susan), Sovio, U. (Ulla), Standl, M. (Marie), Uitterlinden, A.G. (André), Wichmann, E.H. (Erich), Vissing, N.H. (Nadja), DeCarli, C. (Charles), Duijn, C.M. (Cornelia) van, McCarthy, M.I. (M.), Koppelman, G.H. (Gerard), Estivill, X. (Xavier), Hattersley, A.T. (Andrew), Melbye, M. (Mads), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Davey-Smith, G. (George), Heinrich, J. (Joachim), Jarvelin, M.-R. (Marjo-Riitta), and Jaddoe, V.W.V. (Vincent)
Abstract: To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10 -9) and rs1042725 on chromosome 12q15 (P = 2.8 × 10 -10) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10 -7 for rs7980687 and P = 1.3 × 10 -7 for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10 -6). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Published: 2012
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23 results on '"Mcmahon, G. (George)"'

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23. Common variants at 12q15 and 12q24 are associated with infant head circumference

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