Author: "Yaghootkar, H. (Hanieh)" - Searchworks@Jio Institute Digital Library Search Results

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1. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

Author: Vosa, U. (Urmo), Claringbould, A. (Annique), Westra, H.-J. (Harm-Jan), Bonder, M. J. (Marc Jan), Deelen, P. (Patrick), Zeng, B. (Biao), Kirsten, H. (Holger), Saha, A. (Ashis), Kreuzhuber, R. (Roman), Yazar, S. (Seyhan), Brugge, H. (Harm), Oelen, R. (Roy), de Vries, D. H. (Dylan H.), van der Wijst, M. G. (Monique G. P.), Kasela, S. (Silva), Pervjakova, N. (Natalia), Alves, I. (Isabel), Fave, M.-J. (Marie-Julie), Agbessi, M. (Mawusse), Christiansen, M. W. (Mark W.), Jansen, R. (Rick), Seppala, I. (Ilkka), Tong, L. (Lin), Teumer, A. (Alexander), Schramm, K. (Katharina), Hemani, G. (Gibran), Verlouw, J. (Joost), Yaghootkar, H. (Hanieh), Flitman, R. S. (Reyhan Sonmez), Brown, A. (Andrew), Kukushkina, V. (Viktorija), Kalnapenkis, A. (Anette), Rueger, S. (Sina), Porcu, E. (Eleonora), Kronberg, J. (Jaanika), Kettunen, J. (Johannes), Lee, B. (Bernett), Zhang, F. (Futao), Qi, T. (Ting), Hernandez, J. A. (Jose Alquicira), Arindrarto, W. (Wibowo), Beutner, F. (Frank), Dmitrieva, J. (Julia), Elansary, M. (Mahmoud), Fairfax, B. P. (Benjamin P.), Georges, M. (Michel), Heijmans, B. T. (Bastiaan T.), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Kim, Y. (Yungil), Knight, J. C. (Julian C.), Kovacs, P. (Peter), Krohn, K. (Knut), Li, S. (Shuang), Loeffler, M. (Markus), Marigorta, U. M. (Urko M.), Mei, H. (Hailang), Momozawa, Y. (Yukihide), Mueller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. G. (Michel G.), Penninx, B. W. (Brenda W. J. H.), Pritchard, J. K. (Jonathan K.), Raitakari, O. T. (Olli T.), Rotzschke, O. (Olaf), Slagboom, E. P. (Eline P.), Stehouwer, C. D. (Coen D. A.), Stumvoll, M. (Michael), Sullivan, P. (Patrick), Thiery, J. (Joachim), Tonjes, A. (Anke), van Dongen, J. (Jenny), van Iterson, M. (Maarten), Veldink, J. H. (Jan H.), Voelker, U. (Uwe), Warmerdam, R. (Robert), Wijmenga, C. (Cisca), Swertz, M. (Morris), Andiappan, A. (Anand), Montgomery, G. W. (Grant W.), Ripatti, S. (Samuli), Perola, M. (Markus), Kutalik, Z. (Zoltan), Dermitzakis, E. (Emmanouil), Bergmann, S. (Sven), Frayling, T. (Timothy), van Meurs, J. (Joyce), Prokisch, H. (Holger), Ahsan, H. (Habibul), Pierce, B. L. (Brandon L.), Lehtimaki, T. (Terho), Boomsma, D. I. (Dorret, I), Psaty, B. M. (Bruce M.), Gharib, S. A. (Sina A.), Awadalla, P. (Philip), Milani, L. (Lili), Ouwehand, W. H. (Willem H.), Downes, K. (Kate), Stegle, O. (Oliver), Battle, A. (Alexis), Visscher, P. M. (Peter M.), Yang, J. (Jian), Scholz, M. (Markus), Powell, J. (Joseph), Gibson, G. (Greg), Esko, T. (Tonu), Franke, L. (Lude), Vosa, U. (Urmo), Claringbould, A. (Annique), Westra, H.-J. (Harm-Jan), Bonder, M. J. (Marc Jan), Deelen, P. (Patrick), Zeng, B. (Biao), Kirsten, H. (Holger), Saha, A. (Ashis), Kreuzhuber, R. (Roman), Yazar, S. (Seyhan), Brugge, H. (Harm), Oelen, R. (Roy), de Vries, D. H. (Dylan H.), van der Wijst, M. G. (Monique G. P.), Kasela, S. (Silva), Pervjakova, N. (Natalia), Alves, I. (Isabel), Fave, M.-J. (Marie-Julie), Agbessi, M. (Mawusse), Christiansen, M. W. (Mark W.), Jansen, R. (Rick), Seppala, I. (Ilkka), Tong, L. (Lin), Teumer, A. (Alexander), Schramm, K. (Katharina), Hemani, G. (Gibran), Verlouw, J. (Joost), Yaghootkar, H. (Hanieh), Flitman, R. S. (Reyhan Sonmez), Brown, A. (Andrew), Kukushkina, V. (Viktorija), Kalnapenkis, A. (Anette), Rueger, S. (Sina), Porcu, E. (Eleonora), Kronberg, J. (Jaanika), Kettunen, J. (Johannes), Lee, B. (Bernett), Zhang, F. (Futao), Qi, T. (Ting), Hernandez, J. A. (Jose Alquicira), Arindrarto, W. (Wibowo), Beutner, F. (Frank), Dmitrieva, J. (Julia), Elansary, M. (Mahmoud), Fairfax, B. P. (Benjamin P.), Georges, M. (Michel), Heijmans, B. T. (Bastiaan T.), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Kim, Y. (Yungil), Knight, J. C. (Julian C.), Kovacs, P. (Peter), Krohn, K. (Knut), Li, S. (Shuang), Loeffler, M. (Markus), Marigorta, U. M. (Urko M.), Mei, H. (Hailang), Momozawa, Y. (Yukihide), Mueller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. G. (Michel G.), Penninx, B. W. (Brenda W. J. H.), Pritchard, J. K. (Jonathan K.), Raitakari, O. T. (Olli T.), Rotzschke, O. (Olaf), Slagboom, E. P. (Eline P.), Stehouwer, C. D. (Coen D. A.), Stumvoll, M. (Michael), Sullivan, P. (Patrick), Thiery, J. (Joachim), Tonjes, A. (Anke), van Dongen, J. (Jenny), van Iterson, M. (Maarten), Veldink, J. H. (Jan H.), Voelker, U. (Uwe), Warmerdam, R. (Robert), Wijmenga, C. (Cisca), Swertz, M. (Morris), Andiappan, A. (Anand), Montgomery, G. W. (Grant W.), Ripatti, S. (Samuli), Perola, M. (Markus), Kutalik, Z. (Zoltan), Dermitzakis, E. (Emmanouil), Bergmann, S. (Sven), Frayling, T. (Timothy), van Meurs, J. (Joyce), Prokisch, H. (Holger), Ahsan, H. (Habibul), Pierce, B. L. (Brandon L.), Lehtimaki, T. (Terho), Boomsma, D. I. (Dorret, I), Psaty, B. M. (Bruce M.), Gharib, S. A. (Sina A.), Awadalla, P. (Philip), Milani, L. (Lili), Ouwehand, W. H. (Willem H.), Downes, K. (Kate), Stegle, O. (Oliver), Battle, A. (Alexis), Visscher, P. M. (Peter M.), Yang, J. (Jian), Scholz, M. (Markus), Powell, J. (Joseph), Gibson, G. (Greg), Esko, T. (Tonu), and Franke, L. (Lude)
Abstract: Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
Published: 2021

2. Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits

Author: Porcu, E. (Eleonora), Rueger, S. (Sina), Lepik, K. (Kaido), Agbessi, M. (Mawusse), Ahsan, H. (Habibul), Alves, I. (Isabel), Andiappan, A. (Anand), Arindrarto, W. (Wibowo), Awadalla, P. (Philip), Battle, A. (Alexis), Beutner, F. (Frank), Bonder, M. J. (Marc Jan), Boomsma, D. (Dorret), Christiansen, M. (Mark), Claringbould, A. (Annique), Deelen, P. (Patrick), Esko, T. (Tonu), Fave, M.-J. (Marie-Julie), Franke, L. (Lude), Frayling, T. (Timothy), Gharib, S. A. (Sina A.), Gibson, G. (Gregory), Heijmans, B. T. (Bastiaan T.), Hemani, G. (Gibran), Jansen, R. (Rick), Kahonen, M. (Mika), Kalnapenkis, A. (Anette), Kasela, S. (Silva), Kettunen, J. (Johannes), Kim, Y. (Yungil), Kirsten, H. (Holger), Kovacs, P. (Peter), Krohn, K. (Knut), Kronberg-Guzman, J. (Jaanika), Kukushkina, V. (Viktorija), Lee, B. (Bernett), Lehtimaki, T. (Terho), Loeffler, M. (Markus), Marigorta, U. M. (Urko M.), Mei, H. (Hailang), Milani, L. (Lili), Montgomery, G. W. (Grant W.), Mueler-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. (Michel), Penninx, B. (Brenda), Perola, M. (Markus), Pervjakova, N. (Natalia), Pierce, B. L. (Brandon L.), Powell, J. (Joseph), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ripatti, S. (Samuli), Rotzschke, O. (Olaf), Saha, A. (Ashis), Scholz, M. (Markus), Schramm, K. (Katharina), Seppala, I. (Ilkka), Slagboom, E. P. (Eline P.), Stehouwer, C. D. (Coen D. A.), Stumvoll, M. (Michael), Sullivan, P. (Patrick), Teumer, A. (Alexander), Thiery, J. (Joachim), Tong, L. (Lin), Tonjes, A. (Anke), van Dongen, J. (Jenny), van Iterson, M. (Maarten), van Meurs, J. (Joyce), Veldink, J. H. (Jan H.), Verlouw, J. (Joost), Visscher, P. M. (Peter M.), Volker, U. (Uwe), Vosa, U. (Urmo), Westra, H.-J. (Harm-Jan), Wijmenga, C. (Cisca), Yaghootkar, H. (Hanieh), Yang, J. (Jian), Zeng, B. (Biao), Zhang, F. (Futao), Beekman, M. (Marian), Boomsma, D. I. (Dorret I.), Bot, J. (Jan), Deelen, J. (Joris), Hofman, B. A. (Bert A.), Hottenga, J. J. (Jouke J.), Isaacs, A. (Aaron), Jhamai, P. M. (P. Mila), Kielbasa, S. M. (Szymon M.), Lakenberg, N. (Nico), Luijk, R. (Rene), Mei, H. (Hailiang), Moed, M. (Matthijs), Nooren, I. (Irene), Pool, R. (Rene), Schalkwijk, C. G. (Casper G.), Slagboom, P. E. (P. Eline), Suchiman, H. E. (H. Eka D.), Swertz, M. A. (Morris A.), Tigchelaar, E. F. (Ettje F.), Uitterlinden, A. G. (Andre G.), van den Berg, L. H. (Leonard H.), van der Breggen, R. (Ruud), van der Kallen, C. J. (Carla J. H.), van Dijk, F. (Freerk), van Duijn, C. M. (Cornelia M.), van Galen, M. (Michiel), van Greevenbroek, M. M. (Marleen M. J.), van Heemst, D. (Diana), van Rooij, J. (Jeroen), Van't Hof, P. (Peter), van Zwet, E. W. (Erik. W.), Vermaat, M. (Martijn), Verbiest, M. (Michael), Verkerk, M. (Marijn), Zhernakova, D. V. (Dasha V.), Zhernakova, S. (Sasha), Santoni, F. A. (Federico A.), Reymond, A. (Alexandre), and Kutalik, Z. (Zoltan)
Abstract: Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
Published: 2019

3. Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

Author: Jones, S. (S.), van Hees, V.T., Mazzotti, D.R., Marques-Vidal, P. (Pedro), Sabia, S., Spek, A. (Ashley) van der, Dashti, HS, Engmann, J, Kocevska, D. (Desana), Tyrrell, A.W.R., Beaumont, RN, Hillsdon, M., Ruth, KS, Tuke, MA, Yaghootkar, H. (Hanieh), Sharp, S.A., Ji, Y.J., Harrison, J.W., Freathy, R.M. (Rachel), Murray, A. (Anna), Luik, A.I. (Annemarie), Amin, N. (Najaf), Lane, J.M., Saxena, R. (Richa), Rutter, M.K., Tiemeier, H.W. (Henning), Kutalik, Z. (Zoltán), Kumari, M. (Meena), Frayling, T.M. (Timothy), Weedo, M.N. (Michael), Gehrman, P.R. (Philip), Wood, A.R. (Andrew), Jones, S. (S.), van Hees, V.T., Mazzotti, D.R., Marques-Vidal, P. (Pedro), Sabia, S., Spek, A. (Ashley) van der, Dashti, HS, Engmann, J, Kocevska, D. (Desana), Tyrrell, A.W.R., Beaumont, RN, Hillsdon, M., Ruth, KS, Tuke, MA, Yaghootkar, H. (Hanieh), Sharp, S.A., Ji, Y.J., Harrison, J.W., Freathy, R.M. (Rachel), Murray, A. (Anna), Luik, A.I. (Annemarie), Amin, N. (Najaf), Lane, J.M., Saxena, R. (Richa), Rutter, M.K., Tiemeier, H.W. (Henning), Kutalik, Z. (Zoltán), Kumari, M. (Meena), Frayling, T.M. (Timothy), Weedo, M.N. (Michael), Gehrman, P.R. (Philip), and Wood, A.R. (Andrew)
Abstract: Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10−8, of which 20 reach a stricter threshold of P < 8 × 10−10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.
Published: 2019
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4. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Author: Jones, S. (S.), Lane, J.M., Wood, A.R. (Andrew), van Hees, V.T., Tyrrell, A.W.R., Beaumont, RN, Jeffries, A.R., Dashti, HS, Hillsdon, M., Ruth, KS, Tuke, MA, Yaghootkar, H. (Hanieh), Sharp, S.A., Jie, Y.J., Thompson, W.D., Harrison, J.W., Dawes, A., Byrne, E.M. (Enda), Tiemeier, H.W. (Henning), Allebrandt, K.V., Bowden, J., Ray, D.W., Freathy, R.M. (Rachel), Murray, A. (Anna), Mazzotti, D.R., Gehrman, P.R. (Philip), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Rutter, M.K., Hinds, DA, Saxena, R. (Richa), Weedo, M.N. (Michael), Agee, M., Alipanahi, B., Auton, A., Bell, R.K., Bryc, K., Elson, S.L., Fontanillas, P. (Pierre), Furlotte, NA, Huber, K.E., Kleinman, A, Litterman, N.K., McCreight, J.C., McIntyre, M.H., Mountain, J.L., Noblin, E.S., Northover, C.A.M., Pitts, S.J. (Steven), Sathirapongsasuti, JF, Sazonova, O.V., Shelton, J.F., Shringarpure, S., Tian, C, Tung, JY, Vacic, V., Wilson, C.H., Jones, S. (S.), Lane, J.M., Wood, A.R. (Andrew), van Hees, V.T., Tyrrell, A.W.R., Beaumont, RN, Jeffries, A.R., Dashti, HS, Hillsdon, M., Ruth, KS, Tuke, MA, Yaghootkar, H. (Hanieh), Sharp, S.A., Jie, Y.J., Thompson, W.D., Harrison, J.W., Dawes, A., Byrne, E.M. (Enda), Tiemeier, H.W. (Henning), Allebrandt, K.V., Bowden, J., Ray, D.W., Freathy, R.M. (Rachel), Murray, A. (Anna), Mazzotti, D.R., Gehrman, P.R. (Philip), Lawlor, D.A. (Debbie), Frayling, T.M. (Timothy), Rutter, M.K., Hinds, DA, Saxena, R. (Richa), Weedo, M.N. (Michael), Agee, M., Alipanahi, B., Auton, A., Bell, R.K., Bryc, K., Elson, S.L., Fontanillas, P. (Pierre), Furlotte, NA, Huber, K.E., Kleinman, A, Litterman, N.K., McCreight, J.C., McIntyre, M.H., Mountain, J.L., Noblin, E.S., Northover, C.A.M., Pitts, S.J. (Steven), Sathirapongsasuti, JF, Sazonova, O.V., Shelton, J.F., Shringarpure, S., Tian, C, Tung, JY, Vacic, V., and Wilson, C.H.
Published: 2019
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5. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Author: Beaumont, R.N. (Robin N.), Warrington, N.M. (Nicole), Cavadino, A. (Alana), Tyrrell, A.W.R., Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R.C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J.P. (Jonathan), Kreiner-Møller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K.L. (Kathryn), Painter, J.N. (Jodie N.), Hottenga, J.J. (Jouke Jan), Allard, C. (Catherine), Barton, S.J. (Sheila), Espinosa, A. (Ana), Marsh, J.A. (Julie), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W.Q. (Wei), Berry, D. (Diane), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, Ø. (Øyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H.M. (Hazel), Jones, S.E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P.A. (Penelope), Marullo, L. (Letizia), Medland, S.E. (Sarah), Murray, A. (Anna), Murray, J.C. (Jeffrey C.), Njølstad, P.R. (Pa l R.), Nohr, C. (Christian), Reichetzeder, C. (Christoph), Ring, S.M. (Susan), Ruth, K.S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D.M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M.A. (Marcus A.), Vaudel, M. (Marc), Weedon, M.N. (Michael), Willemsen, G.A.H.M. (Gonneke), Wood, A.R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L.J. (Louis J.), Bartels, M. (Meike), Relton, C.L. (Caroline), Pennell, C.E. (Craig), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J.W. (John W.), Boomsma, D.I. (Dorret), Montgomery, G.W. (Grant W.), Murabito, J. (Joanne), Spector, T.D. (Timothy), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S.F.A. (Struan F.A.), Sørensen, T.I.A. (Thorkild I.A.), Jaddoe, V.W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M.I. (Mark I.), Hattersley, A.T. (Andrew), Hayes, M.G. (M. Geoffrey), Frayling, T.M. (Timothy), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Hyppönen, E. (Elina), Lowe, W.L. (William L.), Evans, D.M. (David M.), Lawlor, D.A. (Debbie A.), Feenstra, B. (Bjarke), Freathy, R.M. (Rachel), Beaumont, R.N. (Robin N.), Warrington, N.M. (Nicole), Cavadino, A. (Alana), Tyrrell, A.W.R., Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R.C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J.P. (Jonathan), Kreiner-Møller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K.L. (Kathryn), Painter, J.N. (Jodie N.), Hottenga, J.J. (Jouke Jan), Allard, C. (Catherine), Barton, S.J. (Sheila), Espinosa, A. (Ana), Marsh, J.A. (Julie), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W.Q. (Wei), Berry, D. (Diane), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, Ø. (Øyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H.M. (Hazel), Jones, S.E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P.A. (Penelope), Marullo, L. (Letizia), Medland, S.E. (Sarah), Murray, A. (Anna), Murray, J.C. (Jeffrey C.), Njølstad, P.R. (Pa l R.), Nohr, C. (Christian), Reichetzeder, C. (Christoph), Ring, S.M. (Susan), Ruth, K.S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D.M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M.A. (Marcus A.), Vaudel, M. (Marc), Weedon, M.N. (Michael), Willemsen, G.A.H.M. (Gonneke), Wood, A.R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L.J. (Louis J.), Bartels, M. (Meike), Relton, C.L. (Caroline), Pennell, C.E. (Craig), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J.W. (John W.), Boomsma, D.I. (Dorret), Montgomery, G.W. (Grant W.), Murabito, J. (Joanne), Spector, T.D. (Timothy), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S.F.A. (Struan F.A.), Sørensen, T.I.A. (Thorkild I.A.), Jaddoe, V.W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M.I. (Mark I.), Hattersley, A.T. (Andrew), Hayes, M.G. (M. Geoffrey), Frayling, T.M. (Timothy), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Hyppönen, E. (Elina), Lowe, W.L. (William L.), Evans, D.M. (David M.), Lawlor, D.A. (Debbie A.), Feenstra, B. (Bjarke), and Freathy, R.M. (Rachel)
Abstract: Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of Eu
Published: 2018
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6. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Author: Xue, A. (Angli), Wu, Y. (Yang), Zhu, Z. (Zhihong), Zhang, F. (Futao), Kemper, K.E. (Kathryn E.), Zheng, Z. (Zhili), Yengo, L. (Loic), Lloyd-Jones, L.R. (Luke R.), Sidorenko, J. (Julia), Wu, Y. (Yeda), Agbessi, M. (Mawussé), Ahsan, H. (Habibul), Alves, I. (Isabel), Andiappan, A.K. (Anand Kumar), Awadalla, P. (Philip), Battle, A. (Alexis), Beutner, F. (Frank), Bonder, M.J. (Marc), Boomsma, D. (Dorret), Christiansen, M. (Mark), Claringbould, A. (Annique), Deelen, P. (Patrick), Esko, T. (Tõnu), Favé, M.-J. (Marie-Julie), Franke, L. (Lude), Frayling, T.M. (Timothy), Gharib, S.A. (Sina), Gibson, G. (Gregory), Hemani, G., Jansen, R. (Rick), Kähönen, M. (Mika), Kalnapenkis, A. (Anette), Kasela, S. (Silva), Kettunen, J. (Johannes), Kim, Y. (Yungil), Kirsten, H. (Holger), Kovacs, P. (Peter), Krohn, K. (Knut), Kronberg-Guzman, J. (Jaanika), Kukushkina, V. (Viktorija), Kutalik, Z. (Zoltán), Lee, B. (Bernett), Lehtimäki, T. (Terho), Loeffler, M. (Markus), Marigorta, U.M. (Urko), Metspalu, A. (Andres), Milani, L. (Lili), Müller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. (Michel), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pervjakova, N. (Natalia), Pierce, A. (Andrew), Powell, J. (Joseph), Prokisch, H. (Holger), Psaty, B. (Bruce), Raitakari, O. (Olli), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rotzschke, O. (Olaf), Ruëger, S. (Sina), Saha, A. (Ashis), Scholz, M. (Markus), Schramm, K. (Katharina), Seppälä, I. (Ilkka), Stumvoll, M. (Michael), Sullivan, P.F. (Patrick), Teumer, A. (Alexander), Thiery, J.P. (Joachim), Tong, L. (Lin), Tönjes, A. (Anke), Dongen, J. (Jenny) van, Meurs, J.B.J. (Joyce) van, Verlouw, J.A.M. (Joost), Völker, U. (Uwe), Võsa, U. (Urmo), Yaghootkar, H. (Hanieh), Zeng, B. (Biao), McRae, A.F. (Allan F.), Visscher, P.M. (Peter), Zeng, J. (Jian), Yang, J. (Jian), Xue, A. (Angli), Wu, Y. (Yang), Zhu, Z. (Zhihong), Zhang, F. (Futao), Kemper, K.E. (Kathryn E.), Zheng, Z. (Zhili), Yengo, L. (Loic), Lloyd-Jones, L.R. (Luke R.), Sidorenko, J. (Julia), Wu, Y. (Yeda), Agbessi, M. (Mawussé), Ahsan, H. (Habibul), Alves, I. (Isabel), Andiappan, A.K. (Anand Kumar), Awadalla, P. (Philip), Battle, A. (Alexis), Beutner, F. (Frank), Bonder, M.J. (Marc), Boomsma, D. (Dorret), Christiansen, M. (Mark), Claringbould, A. (Annique), Deelen, P. (Patrick), Esko, T. (Tõnu), Favé, M.-J. (Marie-Julie), Franke, L. (Lude), Frayling, T.M. (Timothy), Gharib, S.A. (Sina), Gibson, G. (Gregory), Hemani, G., Jansen, R. (Rick), Kähönen, M. (Mika), Kalnapenkis, A. (Anette), Kasela, S. (Silva), Kettunen, J. (Johannes), Kim, Y. (Yungil), Kirsten, H. (Holger), Kovacs, P. (Peter), Krohn, K. (Knut), Kronberg-Guzman, J. (Jaanika), Kukushkina, V. (Viktorija), Kutalik, Z. (Zoltán), Lee, B. (Bernett), Lehtimäki, T. (Terho), Loeffler, M. (Markus), Marigorta, U.M. (Urko), Metspalu, A. (Andres), Milani, L. (Lili), Müller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. (Michel), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pervjakova, N. (Natalia), Pierce, A. (Andrew), Powell, J. (Joseph), Prokisch, H. (Holger), Psaty, B. (Bruce), Raitakari, O. (Olli), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rotzschke, O. (Olaf), Ruëger, S. (Sina), Saha, A. (Ashis), Scholz, M. (Markus), Schramm, K. (Katharina), Seppälä, I. (Ilkka), Stumvoll, M. (Michael), Sullivan, P.F. (Patrick), Teumer, A. (Alexander), Thiery, J.P. (Joachim), Tong, L. (Lin), Tönjes, A. (Anke), Dongen, J. (Jenny) van, Meurs, J.B.J. (Joyce) van, Verlouw, J.A.M. (Joost), Völker, U. (Uwe), Võsa, U. (Urmo), Yaghootkar, H. (Hanieh), Zeng, B. (Biao), McRae, A.F. (Allan F.), Visscher, P.M. (Peter), Zeng, J. (Jian), and Yang, J. (Jian)
Abstract: Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.
Published: 2018
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7. Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

Author: Qi, T. (Ting), Wu, Y. (Yang), Zeng, J. (Jian), Zhang, F. (Futao), Xue, A. (Angli), Jiang, L. (Longda), Zhu, Z. (Zhihong), Kemper, K. (Kathryn), Yengo, L. (Loic), Zheng, Z. (Zhili), Agbessi, M. (Mawussé), Ahsan, H. (Habibul), Alves, I. (Isabel), Andiappan, A.K. (Anand Kumar), Awadalla, P. (Philip), Battle, A. (Alexis), Beutner, F. (Frank), Jan Bonder, M. (Marc), Boomsma, D.I. (Dorret), Christiansen, M. (Mark), Claringbould, A. (Annique), Deelen, P. (Patrick), Esko, T. (Tõnu), Favé, M.-J. (Marie-Julie), Franke, L. (Lude), Frayling, T.M. (Timothy), Gharib, S.A. (Sina), Gibson, G. (Gregory), Hemani, G., Jansen, R. (Rick), Kähönen, M. (Mika), Kalnapenkis, A. (Anette), Kasela, S. (Silva), Kettunen, J. (Johannes), Kim, Y. (Yungil), Kirsten, H. (Holger), Kovacs, P. (Peter), Krohn, K. (Knut), Kronberg-Guzman, J. (Jaanika), Kukushkina, V. (Viktorija), Kutalik, Z. (Zoltán), Lee, B. (Bernett), Lehtimäki, T. (Terho), Loeffler, M. (Markus), Marigorta, U.M. (Urko), Metspalu, A. (Andres), Milani, L. (Lili), Müller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. (Michel), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pervjakova, N. (Natalia), Pierce, A. (Andrew), Powell, J. (Joseph), Prokisch, H. (Holger), Psaty, B. (Bruce), Raitakari, O. (Olli), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rotzschke, O. (Olaf), Ruëger, S. (Sina), Saha, A. (Ashis), Scholz, M. (Markus), Schramm, K. (Katharina), Seppälä, I. (Ilkka), Stumvoll, M. (Michael), Sullivan, P.F. (Patrick), Teumer, A. (Alexander), Thiery, J.P. (Joachim), Tong, L. (Lin), Tönjes, A. (Anke), Dongen, J. (Jenny) van, Meurs, J.B.J. (Joyce) van, Verlouw, J.A.M. (Joost), Völker, U. (Uwe), Võsa, U. (Urmo), Yaghootkar, H. (Hanieh), Zeng, B. (Biao), Marioni, R.E. (Riccardo), Montgomery, G.W. (Grant W.), Deary, I.J. (Ian), Wray, N.R. (Naomi R.), Visscher, P.M. (Peter), McRae, A.F. (Allan F.), Yang, J. (Jian), Qi, T. (Ting), Wu, Y. (Yang), Zeng, J. (Jian), Zhang, F. (Futao), Xue, A. (Angli), Jiang, L. (Longda), Zhu, Z. (Zhihong), Kemper, K. (Kathryn), Yengo, L. (Loic), Zheng, Z. (Zhili), Agbessi, M. (Mawussé), Ahsan, H. (Habibul), Alves, I. (Isabel), Andiappan, A.K. (Anand Kumar), Awadalla, P. (Philip), Battle, A. (Alexis), Beutner, F. (Frank), Jan Bonder, M. (Marc), Boomsma, D.I. (Dorret), Christiansen, M. (Mark), Claringbould, A. (Annique), Deelen, P. (Patrick), Esko, T. (Tõnu), Favé, M.-J. (Marie-Julie), Franke, L. (Lude), Frayling, T.M. (Timothy), Gharib, S.A. (Sina), Gibson, G. (Gregory), Hemani, G., Jansen, R. (Rick), Kähönen, M. (Mika), Kalnapenkis, A. (Anette), Kasela, S. (Silva), Kettunen, J. (Johannes), Kim, Y. (Yungil), Kirsten, H. (Holger), Kovacs, P. (Peter), Krohn, K. (Knut), Kronberg-Guzman, J. (Jaanika), Kukushkina, V. (Viktorija), Kutalik, Z. (Zoltán), Lee, B. (Bernett), Lehtimäki, T. (Terho), Loeffler, M. (Markus), Marigorta, U.M. (Urko), Metspalu, A. (Andres), Milani, L. (Lili), Müller-Nurasyid, M. (Martina), Nauck, M. (Matthias), Nivard, M. (Michel), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pervjakova, N. (Natalia), Pierce, A. (Andrew), Powell, J. (Joseph), Prokisch, H. (Holger), Psaty, B. (Bruce), Raitakari, O. (Olli), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rotzschke, O. (Olaf), Ruëger, S. (Sina), Saha, A. (Ashis), Scholz, M. (Markus), Schramm, K. (Katharina), Seppälä, I. (Ilkka), Stumvoll, M. (Michael), Sullivan, P.F. (Patrick), Teumer, A. (Alexander), Thiery, J.P. (Joachim), Tong, L. (Lin), Tönjes, A. (Anke), Dongen, J. (Jenny) van, Meurs, J.B.J. (Joyce) van, Verlouw, J.A.M. (Joost), Völker, U. (Uwe), Võsa, U. (Urmo), Yaghootkar, H. (Hanieh), Zeng, B. (Biao), Marioni, R.E. (Riccardo), Montgomery, G.W. (Grant W.), Deary, I.J. (Ian), Wray, N.R. (Naomi R.), Visscher, P.M. (Peter), McRae, A.F. (Allan F.), and Yang, J. (Jian)
Abstract: Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.
Published: 2018
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8. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Author: Beaumont, R. N. (Robin N.), Warrington, N. M. (Nicole M.), Cavadino, A. (Alana), Tyrrell, J. (Jessica), Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R. C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J. P. (Jonathan P.), Kreiner-Moller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K. L. (Kathryn L.), Painter, J. N. (Jodie N.), Hottenga, J.-J. (Jouke-Jan), Allard, C. (Catherine), Barton, S. J. (Sheila J.), Espinosa, A. (Ana), Marsh, J. A. (Julie A.), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W. (Wei), Berry, D. J. (Diane J.), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, O. (Oyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H. M. (Hazel M.), Jones, S. E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P. A. (Penelope A.), Marullo, L. (Letizia), Medland, S. E. (Sarah E.), Murray, A. (Anna), Murray, J. C. (Jeffrey C.), Njolstad, P. R. (Pal R.), Nohr, E. A. (Ellen A.), Reichetzeder, C. (Christoph), Ring, S. M. (Susan M.), Ruth, K. S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D. M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M. A. (Marcus A.), Vaudel, M. (Marc), Weedon, M. N. (Michael N.), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L. J. (Louis J.), Bartels, M. (Meike), Relton, C. L. (Caroline L.), Pennell, C. E. (Craig E.), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J. W. (John W.), Boomsma, D. I. (Dorret I.), Montgomery, G. W. (Grant W.), Murabito, J. M. (Joanne M.), Spector, T. D. (Tim D.), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S. F. (Struan F. A.), Sorensen, T. I. (Thorkild I. A.), Jaddoe, V. W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M. I. (Mark I.), Hattersley, A. T. (Andrew T.), Hayes, M. G. (M. Geoffrey), Frayling, T. M. (Timothy M.), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Hypponen, E. (Elina), Lowe, W. L. (William L., Jr.), Evans, D. M. (David M.), Lawlor, D. A. (Debbie A.), Feenstra, B. (Bjarke), Freathy, R. M. (Rachel M.), Beaumont, R. N. (Robin N.), Warrington, N. M. (Nicole M.), Cavadino, A. (Alana), Tyrrell, J. (Jessica), Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R. C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J. P. (Jonathan P.), Kreiner-Moller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K. L. (Kathryn L.), Painter, J. N. (Jodie N.), Hottenga, J.-J. (Jouke-Jan), Allard, C. (Catherine), Barton, S. J. (Sheila J.), Espinosa, A. (Ana), Marsh, J. A. (Julie A.), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W. (Wei), Berry, D. J. (Diane J.), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, O. (Oyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H. M. (Hazel M.), Jones, S. E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P. A. (Penelope A.), Marullo, L. (Letizia), Medland, S. E. (Sarah E.), Murray, A. (Anna), Murray, J. C. (Jeffrey C.), Njolstad, P. R. (Pal R.), Nohr, E. A. (Ellen A.), Reichetzeder, C. (Christoph), Ring, S. M. (Susan M.), Ruth, K. S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D. M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M. A. (Marcus A.), Vaudel, M. (Marc), Weedon, M. N. (Michael N.), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L. J. (Louis J.), Bartels, M. (Meike), Relton, C. L. (Caroline L.), Pennell, C. E. (Craig E.), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J. W. (John W.), Boomsma, D. I. (Dorret I.), Montgomery, G. W. (Grant W.), Murabito, J. M. (Joanne M.), Spector, T. D. (Tim D.), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S. F. (Struan F. A.), Sorensen, T. I. (Thorkild I. A.), Jaddoe, V. W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M. I. (Mark I.), Hattersley, A. T. (Andrew T.), Hayes, M. G. (M. Geoffrey), Frayling, T. M. (Timothy M.), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Hypponen, E. (Elina), Lowe, W. L. (William L., Jr.), Evans, D. M. (David M.), Lawlor, D. A. (Debbie A.), Feenstra, B. (Bjarke), and Freathy, R. M. (Rachel M.)
Abstract: Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10−8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Published: 2018

9. Rare and low-frequency coding variants alter human adult height

Author: Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), Lettre, G. (Guillaume), Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), and Lettre, G. (Guillaume)
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of I
Published: 2017
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10. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author: Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), Kutalik, Z. (Zoltán), Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), and Kutalik, Z. (Zoltán)
Abstract: There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increa
Published: 2017
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11. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

Author: Jones, S.E. (Samuel E.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Yaghootkar, H. (Hanieh), Hu, Y. (Youna), Teder-Laving, M. (Maris), Hayward, C. (Caroline), Roenneberg, T., Wilson, J.F. (James F.), Del Greco, F.M. (Fabiola), Hicks, A.A. (Andrew), Shin, C. (Chol), Yun, C.-H. (Chang-Ho), Lee, S.K. (Seung Ku), Metspalu, A. (Andres), Byrne, E.M. (Enda), Gehrman, P.R. (Philip), Tiemeier, H.W. (Henning), Allebrandt, K.V., Freathy, R.M. (Rachel), Murray, A. (Anna), Hinds, D.A. (David A.), Frayling, T.M. (Timothy), Weedon, M.N. (Michael), Jones, S.E. (Samuel E.), Tyrrell, A.W.R., Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Ruth, K.S. (Katherine S.), Tuke, M.A. (Marcus A.), Yaghootkar, H. (Hanieh), Hu, Y. (Youna), Teder-Laving, M. (Maris), Hayward, C. (Caroline), Roenneberg, T., Wilson, J.F. (James F.), Del Greco, F.M. (Fabiola), Hicks, A.A. (Andrew), Shin, C. (Chol), Yun, C.-H. (Chang-Ho), Lee, S.K. (Seung Ku), Metspalu, A. (Andres), Byrne, E.M. (Enda), Gehrman, P.R. (Philip), Tiemeier, H.W. (Henning), Allebrandt, K.V., Freathy, R.M. (Rachel), Murray, A. (Anna), Hinds, D.A. (David A.), Frayling, T.M. (Timothy), and Weedon, M.N. (Michael)
Abstract: Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythm
Published: 2016
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12. 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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13. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author: Scott, R.A. (Robert), Freitag, C.M. (Christine), Li, L. (Li), Chu, A.Y. (Audrey), Surendran, P. (Praveen), Young, R. (Robin), Grarup, N. (Niels), Stancáková, A. (Alena), Chen, Y. (Yuning), Varga, T.V. (Tibor V.), Yaghootkar, H. (Hanieh), Luan, J. (Jian'An), Zhao, J.H. (Jing Hua), Willems, S.M. (Sara), Wessel, J. (Jennifer), Wang, S. (Shuai), Maruthur, N.M. (Nisa M), Michailidou, K. (Kyriaki), Pirie, A. (Ailith), Lee, S.J. (Sven) van der, Gillson, C.J. (Christopher), Al Olama, A.A. (Ali Amin), Amouyel, P. (Philippe), Arriola, L. (Larraitz), Arveiler, D. (Dominique), Aviles-Olmos, I. (Iciar), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Barroso, I.E. (Inês), Garcia, S.B. (Sara Benlloch), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boehnke, M. (Michael), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bork-Jensen, J. (Jette), Bowden, S. (Sarah), Caldas, C. (Carlos), Caslake, M. (Muriel), Cupples, L.A. (Adrienne), Cruchaga, C. (Carlos), Czajkowski, J. (Jacek), Hoed, M. (Marcel) den, Dunn, J.A. (Janet A.), Earl, H. (Helena), Ehret, G.B. (Georg), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Foltynie, T. (Thomas), Ford, I. (Ian), Forouhi, N.G. (Nita), Gianfagna, F. (Francesco), Gonzalez, C. (Carlos), Grioni, S. (Sara), Hiller, L. (Louise), Jansson, J.H., Jørgensen, M.E. (Marit E.), Jukema, J.W. (Jan Wouter), Kaaks, R. (Rudolf), Kee, F. (Frank), Kerrison, N.D. (Nicola D.), Key, T. (Tim), Kontto, J. (Jukka), Kote-Jarai, Z., Kraja, A. (Aldi), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Linneberg, A. (Allan), Liu, C. (Chunyu), Marenne, G. (Gaëlle), Mohlke, K.L. (Karen), Morris, A.P. (Andrew), Muir, K.R. (K.), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Navarro, C. (Carmen), Nielsen, S.F. (Sune), Nilsson, P. (Peter), Nordestgaard, B.G. (Børge), Packard, C.J. (Chris J.), Palli, D. (Domenico), Panico, S. (Salvatore), Peloso, G.M. (Gina), Perola, M. (Markus), Peters, A. (Annette), Poole, C.J. (Christopher J.), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Salomaa, V. (Veikko), Sánchez, M.-J. (María-José), Sattar, N. (Naveed), Sharp, S.J. (Stephen), Sims, R. (Rebecca), Slimani, N. (Nadia), Smith, J.A. (Jennifer A), Thompson, D. (Deborah), Trompet, S. (Stella), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Virtamo, J. (Jarmo), Walker, M. (Mark), Walter, K. (Klaudia), Abraham, J.E. (Jean E.), Amundadottir, L.T. (Laufey T.), Butterworth, A.S. (Adam), Aponte, J.L. (Jennifer L), Dupuis, J. (Josée), Easton, D.F. (Douglas F.), Eeles, R. (Rosalind), Erdmann, J. (Jeanette), Franks, P.W. (Paul), Frayling, T.M. (Timothy), Hansen, T. (T.), Howson, J.M.M. (Joanna M.M.), Jorgensen, T. (Torben), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), McCarthy, M.I. (Mark), Pankow, J.S. (James), Pedersen, O. (Oluf), Riboli, E. (Elio), Rotter, J.I. (Jerome I.), Saleheen, D. (Danish), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Vollenweider, P. (Peter), O'Rahilly, S. (Stephen), Deloukas, P. (Panagiotis), Danesh, J. (John), Goodarzi, M. (Mark), Kathiresan, S. (Sekar), Meigs, J.B. (James), Ehm, M.G. (Margaret G), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Scott, R.A. (Robert), Freitag, C.M. (Christine), Li, L. (Li), Chu, A.Y. (Audrey), Surendran, P. (Praveen), Young, R. (Robin), Grarup, N. (Niels), Stancáková, A. (Alena), Chen, Y. (Yuning), Varga, T.V. (Tibor V.), Yaghootkar, H. (Hanieh), Luan, J. (Jian'An), Zhao, J.H. (Jing Hua), Willems, S.M. (Sara), Wessel, J. (Jennifer), Wang, S. (Shuai), Maruthur, N.M. (Nisa M), Michailidou, K. (Kyriaki), Pirie, A. (Ailith), Lee, S.J. (Sven) van der, Gillson, C.J. (Christopher), Al Olama, A.A. (Ali Amin), Amouyel, P. (Philippe), Arriola, L. (Larraitz), Arveiler, D. (Dominique), Aviles-Olmos, I. (Iciar), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Barroso, I.E. (Inês), Garcia, S.B. (Sara Benlloch), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boehnke, M. (Michael), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bork-Jensen, J. (Jette), Bowden, S. (Sarah), Caldas, C. (Carlos), Caslake, M. (Muriel), Cupples, L.A. (Adrienne), Cruchaga, C. (Carlos), Czajkowski, J. (Jacek), Hoed, M. (Marcel) den, Dunn, J.A. (Janet A.), Earl, H. (Helena), Ehret, G.B. (Georg), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Foltynie, T. (Thomas), Ford, I. (Ian), Forouhi, N.G. (Nita), Gianfagna, F. (Francesco), Gonzalez, C. (Carlos), Grioni, S. (Sara), Hiller, L. (Louise), Jansson, J.H., Jørgensen, M.E. (Marit E.), Jukema, J.W. (Jan Wouter), Kaaks, R. (Rudolf), Kee, F. (Frank), Kerrison, N.D. (Nicola D.), Key, T. (Tim), Kontto, J. (Jukka), Kote-Jarai, Z., Kraja, A. (Aldi), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Linneberg, A. (Allan), Liu, C. (Chunyu), Marenne, G. (Gaëlle), Mohlke, K.L. (Karen), Morris, A.P. (Andrew), Muir, K.R. (K.), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Navarro, C. (Carmen), Nielsen, S.F. (Sune), Nilsson, P. (Peter), Nordestgaard, B.G. (Børge), Packard, C.J. (Chris J.), Palli, D. (Domenico), Panico, S. (Salvatore), Peloso, G.M. (Gina), Perola, M. (Markus), Peters, A. (Annette), Poole, C.J. (Christopher J.), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Salomaa, V. (Veikko), Sánchez, M.-J. (María-José), Sattar, N. (Naveed), Sharp, S.J. (Stephen), Sims, R. (Rebecca), Slimani, N. (Nadia), Smith, J.A. (Jennifer A), Thompson, D. (Deborah), Trompet, S. (Stella), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Virtamo, J. (Jarmo), Walker, M. (Mark), Walter, K. (Klaudia), Abraham, J.E. (Jean E.), Amundadottir, L.T. (Laufey T.), Butterworth, A.S. (Adam), Aponte, J.L. (Jennifer L), Dupuis, J. (Josée), Easton, D.F. (Douglas F.), Eeles, R. (Rosalind), Erdmann, J. (Jeanette), Franks, P.W. (Paul), Frayling, T.M. (Timothy), Hansen, T. (T.), Howson, J.M.M. (Joanna M.M.), Jorgensen, T. (Torben), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), McCarthy, M.I. (Mark), Pankow, J.S. (James), Pedersen, O. (Oluf), Riboli, E. (Elio), Rotter, J.I. (Jerome I.), Saleheen, D. (Danish), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Vollenweider, P. (Peter), O'Rahilly, S. (Stephen), Deloukas, P. (Panagiotis), Danesh, J. (John), Goodarzi, M. (Mark), Kathiresan, S. (Sekar), Meigs, J.B. (James), Ehm, M.G. (Margaret G), Wareham, N.J. (Nick), and Waterworth, D. (Dawn)
Abstract: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11, 806 individuals by targeted exome sequencing and follow-up in 39, 979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
Published: 2016
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14. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author: Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), Munroe, P. (Patricia), Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), and Munroe, P. (Patricia)
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Published: 2016
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15. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author: Wessel, J. (Jennifer), Chu, A.Y. (Audrey Y), Willems, S.M. (Sara), Wang, S. (Shuai), Yaghootkar, H. (Hanieh), Brody, J.A. (Jennifer A.), Dauriz, M. (Marco), Hivert, M.-F. (Marie-France), Raghavan, S. (Sridharan), Lipovich, L. (Leonard), Hidalgo, B. (Bertha), Fox, K. (Keolu), Huffman, J.E. (Jennifer), An, P. (Ping), Lu, Y. (Yingchang), Rasmussen-Torvik, L.J. (Laura), Grarup, N. (Niels), Ehm, M.G. (Margaret G), L. Li, Baldridge, A.S. (Abigail S), Stancáková, A. (Alena), Abrol, R. (Ravinder), Besse, C. (Céline), Boland, A. (Anne), Bork-Jensen, J. (Jette), Fornage, M. (Myriam), Freitag, C.M. (Christine), Garcia, M. (Melissa), Guo, X. (Xiuqing), Hara, K. (Kazuo), Isaacs, A. (Aaron), Jakobsdottir, M. (Margret), Lange, L.A. (Leslie), Layton, J.C. (Jill C), Li, M. (Man), Zhao, J.H. (Jing Hua), Meidtner, K. (Karina), Morrison, A.C. (Alanna), Nalls, M.A. (Michael), Peters, M.J. (Marjolein), Sabater-Lleal, M. (Maria), Schurmann, C. (Claudia), Silveira, A. (Angela), Smith, A.V. (Davey), Southam, L. (Lorraine), Stoiber, M.H. (Marcus H), Strawbridge, R.J. (Rona), Taylor, K.D. (Kent), Varga, T.V. (Tibor V.), Allin, K.H. (Kristine H), Amin, N. (Najaf), Aponte, J.L. (Jennifer L), Aung, T. (Tin), Barbieri, C. (Caterina), Bihlmeyer, N.A. (Nathan A.), Boehnke, M. (Michael), Bombieri, C. (Cristina), Bowden, D.W. (Donald), Burns, S.M. (Sean M), Chen, Y. (Yuning), Chen, Y.-D. (Yii-Deri), Cheng, C-Y. (Ching-Yu), Correa, D.D., Czajkowski, J. (Jacek), Dehghan, A. (Abbas), Ehret, G.B. (Georg), Eiriksdottir, G. (Gudny), Escher, S.A. (Stefan A), Farmaki, A.-E. (Aliki-Eleni), Frånberg, M. (Mattias), Gambaro, G. (Giovanni), Giulianini, F. (Franco), Goddard, W.A. (William A), Goel, A. (Anuj), Gottesman, R.F. (Rebecca), Grove, M.L. (Megan), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hallmans, G. (Göran), Heo, J. (Jiyoung), Hoffmann, P. (Per), Ikram, M.K. (Kamran), Jensen, R.A. (Richard), Jørgensen, M.E. (Marit), Jorgensen, T. (Torben), Karaleftheri, M. (Maria), Khor, C.C., Kirkpatrick, A. (Andrea), Kraja, A. (Aldi), Kuusisto, J. (Johanna), Lange, E.M. (Ethan), Lee, I.T., Lee, W.-J. (Wen-Jane), Leong, A. (Aaron), Liao, J. (Jie), Liu, C. (Chunyu), Liu, Y. (YongMei), Lindgren, C.M. (Cecilia), Linneberg, A. (Allan), Malerba, G. (Giovanni), Mamakou, V. (Vasiliki), Marouli, E. (Eirini), Maruthur, N.M. (Nisa M), Matchan, A. (Angela), McKean-Cowdin, R. (Roberta), McLeod, O. (Olga), Metcalf, G.A. (Ginger A.), Mohlke, K.L. (Karen), Muzny, D. (Donna), Ntalla, I. (Ioanna), Palmer, N.D. (Nicholette), Pasko, D. (Dorota), Peter, A. (Andreas), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rice, K.M. (Kenneth), Sala, C. (Cinzia), Sennblad, B. (Bengt), Serafetinidis, I. (Ioannis), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Speliotes, E.K. (Elizabeth), Stahl, E.A. (Eli), Stirrups, K. (Kathy), Tentolouris, N. (Nikos), Thanopoulou, A. (Anastasia), Torres, M. (Mina), Traglia, M. (Michela), Tsafantakis, E. (Emmanouil), Javad, S. (Sundas), Yanek, L.R. (Lisa), Zengini, E. (Eleni), Becker, D.M. (Diane), Bis, J.C. (Joshua), Brown, J.B. (James B), Cupples, L.A. (Adrienne), Hansen, T. (T.), Ingelsson, E. (Erik), Karter, A.J. (Andrew J), Lorenzo, C. (Carlos), Mathias, J. (Jasmine), Norris, J.M. (Jill M), Peloso, G.M. (Gina), Sheu, W.H.-H. (Wayne H.-H.), Toniolo, D. (Daniela), Vaidya, D. (Dhananjay), Varma, R. (Rohit), Wagenknecht, L.E. (Lynne), Boeing, H. (Heiner), Bottinger, E.P. (Erwin P.), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Ferrannini, E. (Ele), Franco, O.H. (Oscar), Franks, P.W. (Paul), Gibbs, R.A. (Richard A), Gudnason, V. (Vilmundur), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), Hofman, A. (Albert), Jansson, J.-H. (Jan-Håkan), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Levy, D. (Daniel), Oostra, B.A. (Ben), O'Donnell, C.J. (Christopher J.), O'Rahilly, S. (Stephen), Padmanabhan, S. (Sandosh), Pankow, J.S. (James), Polasek, O. (Ozren), Province, M.A. (Mike), Rich, S.S. (Stephen S.), Ridker, P.M. (Paul), Rudan, I. (Igor), Schulze, M.B. (Matthias B), Smith, B.H. (Blair), Uitterlinden, A.G. (André), Walker, M. (Mark), Watkins, H. (Hugh), Wong, T.Y. (Tien Yin), Zeggini, E. (Eleftheria), Laakso, M. (Markku), Borecki, I.B. (Ingrid), Chasman, D.I. (Daniel), Pedersen, O. (Oluf), Psaty, B.M. (Bruce), Shyong Tai, E., Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Waterworth, D.M. (Dawn), Boerwinkle, E.A. (Eric), Kao, W.H.L. (Wen), Florez, J.C. (Jose), Loos, R.J.F. (Ruth), Wilson, J.G. (James), Frayling, T.M. (Timothy M.), Siscovick, D.S. (David), Dupuis, J. (Josée), Rotter, J.I. (Jerome I.), Meigs, J.B. (James), Scott, R.A. (Robert), Goodarzi, M. (Mark), Wessel, J. (Jennifer), Chu, A.Y. (Audrey Y), Willems, S.M. (Sara), Wang, S. (Shuai), Yaghootkar, H. (Hanieh), Brody, J.A. (Jennifer A.), Dauriz, M. (Marco), Hivert, M.-F. (Marie-France), Raghavan, S. (Sridharan), Lipovich, L. (Leonard), Hidalgo, B. (Bertha), Fox, K. (Keolu), Huffman, J.E. (Jennifer), An, P. (Ping), Lu, Y. (Yingchang), Rasmussen-Torvik, L.J. (Laura), Grarup, N. (Niels), Ehm, M.G. (Margaret G), L. Li, Baldridge, A.S. (Abigail S), Stancáková, A. (Alena), Abrol, R. (Ravinder), Besse, C. (Céline), Boland, A. (Anne), Bork-Jensen, J. (Jette), Fornage, M. (Myriam), Freitag, C.M. (Christine), Garcia, M. (Melissa), Guo, X. (Xiuqing), Hara, K. (Kazuo), Isaacs, A. (Aaron), Jakobsdottir, M. (Margret), Lange, L.A. (Leslie), Layton, J.C. (Jill C), Li, M. (Man), Zhao, J.H. (Jing Hua), Meidtner, K. (Karina), Morrison, A.C. (Alanna), Nalls, M.A. (Michael), Peters, M.J. (Marjolein), Sabater-Lleal, M. (Maria), Schurmann, C. (Claudia), Silveira, A. (Angela), Smith, A.V. (Davey), Southam, L. (Lorraine), Stoiber, M.H. (Marcus H), Strawbridge, R.J. (Rona), Taylor, K.D. (Kent), Varga, T.V. (Tibor V.), Allin, K.H. (Kristine H), Amin, N. (Najaf), Aponte, J.L. (Jennifer L), Aung, T. (Tin), Barbieri, C. (Caterina), Bihlmeyer, N.A. (Nathan A.), Boehnke, M. (Michael), Bombieri, C. (Cristina), Bowden, D.W. (Donald), Burns, S.M. (Sean M), Chen, Y. (Yuning), Chen, Y.-D. (Yii-Deri), Cheng, C-Y. (Ching-Yu), Correa, D.D., Czajkowski, J. (Jacek), Dehghan, A. (Abbas), Ehret, G.B. (Georg), Eiriksdottir, G. (Gudny), Escher, S.A. (Stefan A), Farmaki, A.-E. (Aliki-Eleni), Frånberg, M. (Mattias), Gambaro, G. (Giovanni), Giulianini, F. (Franco), Goddard, W.A. (William A), Goel, A. (Anuj), Gottesman, R.F. (Rebecca), Grove, M.L. (Megan), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hallmans, G. (Göran), Heo, J. (Jiyoung), Hoffmann, P. (Per), Ikram, M.K. (Kamran), Jensen, R.A. (Richard), Jørgensen, M.E. (Marit), Jorgensen, T. (Torben), Karaleftheri, M. (Maria), Khor, C.C., Kirkpatrick, A. (Andrea), Kraja, A. (Aldi), Kuusisto, J. (Johanna), Lange, E.M. (Ethan), Lee, I.T., Lee, W.-J. (Wen-Jane), Leong, A. (Aaron), Liao, J. (Jie), Liu, C. (Chunyu), Liu, Y. (YongMei), Lindgren, C.M. (Cecilia), Linneberg, A. (Allan), Malerba, G. (Giovanni), Mamakou, V. (Vasiliki), Marouli, E. (Eirini), Maruthur, N.M. (Nisa M), Matchan, A. (Angela), McKean-Cowdin, R. (Roberta), McLeod, O. (Olga), Metcalf, G.A. (Ginger A.), Mohlke, K.L. (Karen), Muzny, D. (Donna), Ntalla, I. (Ioanna), Palmer, N.D. (Nicholette), Pasko, D. (Dorota), Peter, A. (Andreas), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rice, K.M. (Kenneth), Sala, C. (Cinzia), Sennblad, B. (Bengt), Serafetinidis, I. (Ioannis), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Speliotes, E.K. (Elizabeth), Stahl, E.A. (Eli), Stirrups, K. (Kathy), Tentolouris, N. (Nikos), Thanopoulou, A. (Anastasia), Torres, M. (Mina), Traglia, M. (Michela), Tsafantakis, E. (Emmanouil), Javad, S. (Sundas), Yanek, L.R. (Lisa), Zengini, E. (Eleni), Becker, D.M. (Diane), Bis, J.C. (Joshua), Brown, J.B. (James B), Cupples, L.A. (Adrienne), Hansen, T. (T.), Ingelsson, E. (Erik), Karter, A.J. (Andrew J), Lorenzo, C. (Carlos), Mathias, J. (Jasmine), Norris, J.M. (Jill M), Peloso, G.M. (Gina), Sheu, W.H.-H. (Wayne H.-H.), Toniolo, D. (Daniela), Vaidya, D. (Dhananjay), Varma, R. (Rohit), Wagenknecht, L.E. (Lynne), Boeing, H. (Heiner), Bottinger, E.P. (Erwin P.), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Ferrannini, E. (Ele), Franco, O.H. (Oscar), Franks, P.W. (Paul), Gibbs, R.A. (Richard A), Gudnason, V. (Vilmundur), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), Hofman, A. (Albert), Jansson, J.-H. (Jan-Håkan), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Levy, D. (Daniel), Oostra, B.A. (Ben), O'Donnell, C.J. (Christopher J.), O'Rahilly, S. (Stephen), Padmanabhan, S. (Sandosh), Pankow, J.S. (James), Polasek, O. (Ozren), Province, M.A. (Mike), Rich, S.S. (Stephen S.), Ridker, P.M. (Paul), Rudan, I. (Igor), Schulze, M.B. (Matthias B), Smith, B.H. (Blair), Uitterlinden, A.G. (André), Walker, M. (Mark), Watkins, H. (Hugh), Wong, T.Y. (Tien Yin), Zeggini, E. (Eleftheria), Laakso, M. (Markku), Borecki, I.B. (Ingrid), Chasman, D.I. (Daniel), Pedersen, O. (Oluf), Psaty, B.M. (Bruce), Shyong Tai, E., Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Waterworth, D.M. (Dawn), Boerwinkle, E.A. (Eric), Kao, W.H.L. (Wen), Florez, J.C. (Jose), Loos, R.J.F. (Ruth), Wilson, J.G. (James), Frayling, T.M. (Timothy M.), Siscovick, D.S. (David), Dupuis, J. (Josée), Rotter, J.I. (Jerome I.), Meigs, J.B. (James), Scott, R.A. (Robert), and Goodarzi, M. (Mark)
Published: 2015
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16. Cell Specific eQTL Analysis without Sorting Cells

Author: Westra, H.J. (Harm-Jan), Arends, D. (Danny), Esko, T. (Tõnu), Peters, M.J. (Marjolein), Schurmann, C. (Claudia), Schramm, K. (Katharina), Kettunen, J. (Johannes), Yaghootkar, H. (Hanieh), Fairfax, B.P. (Benjamin), Andiappan, A.K. (Anand Kumar), Li, Y. (Yang), Fu, J. (Jingyuan), Karjalainen, J. (Juha), Platteel, I. (Inge), Visschedijk, M. (Marijn), Weersma, R.K. (Rinse K.), Kasela, S. (Silva), Milani, L. (Lili), Tserel, L. (Liina), Peterson, P. (Pärt), Reinmaa, E. (Eva), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Homuth, G. (Georg), Petersmann, A. (Astrid), Lorbeer, R. (Roberto), Prokisch, H. (Holger), Meitinger, T. (Thomas), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Ripatti, S. (Samuli), Perola, M. (Markus), Wood, A.R. (Andrew), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Knight, J.C. (Julian), Melchiotti, R. (Rossella), Lee, B. (Bernett), Poidinger, M. (Michael), Zolezzi, F. (Francesca), Larbi, A. (Anis), Wang, D.Y. (De Yun), Berg, L.H. (Leonard) van den, Veldink, J.H. (Jan), Rotzschke, O. (Olaf), Makino, S. (Seiko), Salomaa, V. (Veikko), Strauch, K. (Konstantin), Völker, U. (Uwe), Meurs, J.B.J. (Joyce) van, Metspalu, A. (Andres), Wijmenga, C. (Cisca), Jansen, R.C. (Ritsert), Franke, L. (Lude), Westra, H.J. (Harm-Jan), Arends, D. (Danny), Esko, T. (Tõnu), Peters, M.J. (Marjolein), Schurmann, C. (Claudia), Schramm, K. (Katharina), Kettunen, J. (Johannes), Yaghootkar, H. (Hanieh), Fairfax, B.P. (Benjamin), Andiappan, A.K. (Anand Kumar), Li, Y. (Yang), Fu, J. (Jingyuan), Karjalainen, J. (Juha), Platteel, I. (Inge), Visschedijk, M. (Marijn), Weersma, R.K. (Rinse K.), Kasela, S. (Silva), Milani, L. (Lili), Tserel, L. (Liina), Peterson, P. (Pärt), Reinmaa, E. (Eva), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Homuth, G. (Georg), Petersmann, A. (Astrid), Lorbeer, R. (Roberto), Prokisch, H. (Holger), Meitinger, T. (Thomas), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Ripatti, S. (Samuli), Perola, M. (Markus), Wood, A.R. (Andrew), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Knight, J.C. (Julian), Melchiotti, R. (Rossella), Lee, B. (Bernett), Poidinger, M. (Michael), Zolezzi, F. (Francesca), Larbi, A. (Anis), Wang, D.Y. (De Yun), Berg, L.H. (Leonard) van den, Veldink, J.H. (Jan), Rotzschke, O. (Olaf), Makino, S. (Seiko), Salomaa, V. (Veikko), Strauch, K. (Konstantin), Völker, U. (Uwe), Meurs, J.B.J. (Joyce) van, Metspalu, A. (Andres), Wijmenga, C. (Cisca), Jansen, R.C. (Ritsert), and Franke, L. (Lude)
Abstract: The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.
Published: 2015
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17. The transcriptional landscape of age in human peripheral blood

Author: Peters, M.J. (Marjolein), Joehanes, R. (Roby), Pilling, L.C. (Luke), Schurmann, C. (Claudia), Conneely, K.N. (Karen N.), Powell, J.E. (Joseph), Reinmaa, E. (Eva), Sutphin, G.L. (George L.), Zhernakova, A. (Alexandra), Schramm, K. (Katharina), Wilson, Y.A. (Yana A.), Kobes, S. (Sayuko), Tukiainen, T. (Taru), Ramos, Y.F.M. (Yolande), Göring, H.H.H. (Harald H.), Fornage, M. (Myriam), Liu, Y. (YongMei), Gharib, S.A. (Sina), Stranger, B.E. (Barbara), Jager, P.L. (Philip) de, Aviv, A. (Abraham), Levy, D. (Daniel), Murabito, J. (Joanne), Munson, P.J. (Peter J.), Huan, T. (Tianxiao), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Rooij, J.G.J. (Jeroen) van, Stolk, L. (Lisette), Broer, L. (Linda), Verbiest, M.M.P.J. (Michael), Jhamai, M. (Mila), Arp, P.P. (Pascal), Metspalu, A. (Andres), Tserel, L. (Liina), Milani, L. (Lili), Samani, N.J. (Nilesh), Peterson, P. (Pärt), Kasela, S. (Silva), Codd, V. (Veryan), Peters, A. (Annette), Ward-Caviness, C.K. (Cavin K.), Herder, C. (Christian), Waldenberger, M. (Melanie), Roden, M. (Michael), Singmann, P. (Paula), Zeilinger, S. (Sonja), Illig, T. (Thomas), Homuth, G. (Georg), Grabe, H.J. (Hans Jörgen), Völzke, H. (Henry), Steil, L. (Leif), Kocher, T. (Thomas), Murray, A. (Anna), Melzer, D. (David), Yaghootkar, H. (Hanieh), Bandinelli, S., Moses, E.K. (Eric), Kent, J.W. (Jack), Curran, J.E. (Joanne), Johnson, M.P. (Matthew), Williams-Blangero, S. (Sarah), Westra, H.J. (Harm-Jan), McRae, A.F. (Allan F.), Smith, J.A. (Jennifer A), Kardia, S.L.R. (Sharon), Hovatta, I. (Iiris), Perola, M. (Markus), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Henders, A.K. (Anjali), Martin, N.G. (Nicholas), Smith, A.K. (Alicia K.), Mehta, D. (Divya), Binder, E.B. (Elisabeth B.), Nylocks, K.M. (K. Maria), Kennedy, E.M. (Elizabeth M.), Klengel, T. (Torsten), Ding, J. (Jingzhong), Suchy-Dicey, A. (Astrid), Enquobahrie, D., Brody, J.A. (Jennifer A.), Rotter, J.I. (Jerome I.), Chen, Y.-D.I. (Yii-Der I.), Houwing-Duistermaat, J.J. (Jeanine), Kloppenburg, M. (Margreet), Slagboom, P.E. (Eline), Helmer, Q. (Quinta), Hollander, W. (Wouter) den, Bean, S. (Shannon), Raj, T. (Towfique), Bakhshi, N. (Noman), Wang, Q.P. (Qiao Ping), Oyston, L.J. (Lisa J.), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Montgomery, G.W. (Grant), Turner, S.T. (Stephen), Blangero, J. (John), Meulenbelt, I. (Ingrid), Ressler, K.J. (Kerry), Yang, J. (Jian), Franke, L. (Lude), Kettunen, J. (Johannes), Visscher, P.M. (Peter), Neely, G.G. (G. Gregory), Korstanje, R. (Ron), Hanson, R.L. (Robert L.), Prokisch, H. (Holger), Ferrucci, L. (Luigi), Esko, T. (Tõnu), Teumer, A. (Alexander), Meurs, J.B.J. (Joyce) van, Johnson, A.D. (Andrew D.), Nalls, M.A. (Michael), Hernandez, D.G. (Dena), Cookson, M.R. (Mark), Gibbs, R.J. (Raphael J.), Hardy, J. (John), Ramasamy, A. (Adaikalavan), Zonderman, A.B. (Alan B.), Dillman, A. (Allissa), Traynor, B. (Bryan), Smith, C. (Colin), Longo, D.L. (Dan L.), Trabzuni, D. (Danyah), Troncoso, J.C. (Juan), Brug, M.P. (Marcel) van der, Weale, M.E. (Michael), O'Brien, R. (Richard), Johnson, R. (Robert), Walker, R. (Robert), Zielke, R.H. (Ronald H.), Arepalli, S. (Sampath), Ryten, M. (Mina), Singleton, A., Peters, M.J. (Marjolein), Joehanes, R. (Roby), Pilling, L.C. (Luke), Schurmann, C. (Claudia), Conneely, K.N. (Karen N.), Powell, J.E. (Joseph), Reinmaa, E. (Eva), Sutphin, G.L. (George L.), Zhernakova, A. (Alexandra), Schramm, K. (Katharina), Wilson, Y.A. (Yana A.), Kobes, S. (Sayuko), Tukiainen, T. (Taru), Ramos, Y.F.M. (Yolande), Göring, H.H.H. (Harald H.), Fornage, M. (Myriam), Liu, Y. (YongMei), Gharib, S.A. (Sina), Stranger, B.E. (Barbara), Jager, P.L. (Philip) de, Aviv, A. (Abraham), Levy, D. (Daniel), Murabito, J. (Joanne), Munson, P.J. (Peter J.), Huan, T. (Tianxiao), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Rooij, J.G.J. (Jeroen) van, Stolk, L. (Lisette), Broer, L. (Linda), Verbiest, M.M.P.J. (Michael), Jhamai, M. (Mila), Arp, P.P. (Pascal), Metspalu, A. (Andres), Tserel, L. (Liina), Milani, L. (Lili), Samani, N.J. (Nilesh), Peterson, P. (Pärt), Kasela, S. (Silva), Codd, V. (Veryan), Peters, A. (Annette), Ward-Caviness, C.K. (Cavin K.), Herder, C. (Christian), Waldenberger, M. (Melanie), Roden, M. (Michael), Singmann, P. (Paula), Zeilinger, S. (Sonja), Illig, T. (Thomas), Homuth, G. (Georg), Grabe, H.J. (Hans Jörgen), Völzke, H. (Henry), Steil, L. (Leif), Kocher, T. (Thomas), Murray, A. (Anna), Melzer, D. (David), Yaghootkar, H. (Hanieh), Bandinelli, S., Moses, E.K. (Eric), Kent, J.W. (Jack), Curran, J.E. (Joanne), Johnson, M.P. (Matthew), Williams-Blangero, S. (Sarah), Westra, H.J. (Harm-Jan), McRae, A.F. (Allan F.), Smith, J.A. (Jennifer A), Kardia, S.L.R. (Sharon), Hovatta, I. (Iiris), Perola, M. (Markus), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Henders, A.K. (Anjali), Martin, N.G. (Nicholas), Smith, A.K. (Alicia K.), Mehta, D. (Divya), Binder, E.B. (Elisabeth B.), Nylocks, K.M. (K. Maria), Kennedy, E.M. (Elizabeth M.), Klengel, T. (Torsten), Ding, J. (Jingzhong), Suchy-Dicey, A. (Astrid), Enquobahrie, D., Brody, J.A. (Jennifer A.), Rotter, J.I. (Jerome I.), Chen, Y.-D.I. (Yii-Der I.), Houwing-Duistermaat, J.J. (Jeanine), Kloppenburg, M. (Margreet), Slagboom, P.E. (Eline), Helmer, Q. (Quinta), Hollander, W. (Wouter) den, Bean, S. (Shannon), Raj, T. (Towfique), Bakhshi, N. (Noman), Wang, Q.P. (Qiao Ping), Oyston, L.J. (Lisa J.), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Montgomery, G.W. (Grant), Turner, S.T. (Stephen), Blangero, J. (John), Meulenbelt, I. (Ingrid), Ressler, K.J. (Kerry), Yang, J. (Jian), Franke, L. (Lude), Kettunen, J. (Johannes), Visscher, P.M. (Peter), Neely, G.G. (G. Gregory), Korstanje, R. (Ron), Hanson, R.L. (Robert L.), Prokisch, H. (Holger), Ferrucci, L. (Luigi), Esko, T. (Tõnu), Teumer, A. (Alexander), Meurs, J.B.J. (Joyce) van, Johnson, A.D. (Andrew D.), Nalls, M.A. (Michael), Hernandez, D.G. (Dena), Cookson, M.R. (Mark), Gibbs, R.J. (Raphael J.), Hardy, J. (John), Ramasamy, A. (Adaikalavan), Zonderman, A.B. (Alan B.), Dillman, A. (Allissa), Traynor, B. (Bryan), Smith, C. (Colin), Longo, D.L. (Dan L.), Trabzuni, D. (Danyah), Troncoso, J.C. (Juan), Brug, M.P. (Marcel) van der, Weale, M.E. (Michael), O'Brien, R. (Richard), Johnson, R. (Robert), Walker, R. (Robert), Zielke, R.H. (Ronald H.), Arepalli, S. (Sampath), Ryten, M. (Mina), and Singleton, A.
Abstract: Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
Published: 2015
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18. A Genetic variant in the seed region of miR-4513 shows pleiotropic effects on lipid and glucose homeostasis, blood pressure, and coronary artery disease

Author: Ghanbari, M. (Mohsen), Vries, P.S. (Paul) de, Looper, H. (Hans) de, Peters, M.J. (Marjolein), Schurmann, C. (Claudia), Yaghootkar, H. (Hanieh), Dörr, M. (Marcus), Frayling, T.M. (Timothy), Uitterlinden, A.G. (André), Hofman, A. (Albert), Meurs, J.B.J. (Joyce) van, Erkeland, S.J. (Stefan), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Ghanbari, M. (Mohsen), Vries, P.S. (Paul) de, Looper, H. (Hans) de, Peters, M.J. (Marjolein), Schurmann, C. (Claudia), Yaghootkar, H. (Hanieh), Dörr, M. (Marcus), Frayling, T.M. (Timothy), Uitterlinden, A.G. (André), Hofman, A. (Albert), Meurs, J.B.J. (Joyce) van, Erkeland, S.J. (Stefan), Franco, O.H. (Oscar), and Dehghan, A. (Abbas)
Abstract: MicroRNAs (miRNA) play a crucial role in the regulation of diverse biological processes by post-transcriptional modulation of gene expression. Genetic polymorphisms in miRNA-related genes can potentially contribute to a wide range of phenotypes. The effect of such variants on cardiometabolic diseases has not yet been defined. We systematically investigated the association of genetic variants in the seed region of miRNAs with cardiometabolic phenotypes, using the thus far largest genome-wide association studies on 17 cardiometabolic traits/diseases. We found that rs2168518:G>A, a seed region variant of miR-4513, associates with fasting glucose, low-density lipoprotein-cholesterol, total cholesterol, systolic and diastolic blood pressure, and risk of coronary artery disease. We experimentally showed that miR-4513 expression is significantly reduced in the presence of the rs2168518 mutant allele. We sought to identify miR-4513
Published: 2014
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19. Systematic identification of trans eQTLs as putative drivers of known disease associations

Author: Westra, H.J. (Harm-Jan), Peters, M.J. (Marjolein), Esko, T. (Tõnu), Yaghootkar, H. (Hanieh), Schurmann, C. (Claudia), Kettunen, J. (Johannes), Christiansen, M.W. (Mark), Fairfax, B.P. (Benjamin), Schramm, K. (Katharina), Powell, J.E. (Joseph), Zhernakova, A. (Alexandra), Veldink, J.H. (Jan), Berg, L.H. (Leonard) van den, Karjalainen, J. (Juha), Withoff, S. (Sebo), Uitterlinden, A.G. (André), Hofman, B., Rivadeneira Ramirez, F. (Fernando), Hoen, P.A.C. (Peter) 't, Reinmaa, E. (Eva), Fischer, K. (Kathelijn), Nelis, M. (Mari), Milani, A.L. (Alfredo), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A.B. (Andrew), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Homuth, G. (Georg), Nauck, M.A. (Matthias), Radke, D. (Dörte), Vol̈ker, U. (Uwe), Perola, M. (Markus), Salomaa, V. (Veikko), Brody, J.A. (Jennifer A.), Suchy-Dicey, A. (Astrid), Gharib, S.A. (Sina), Enquobahrie, D., Lumley, T. (Thomas), Montgomery, G.W., Makino, S. (Seiko), Prokisch, H. (Holger), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Meitinger, T. (Thomas), Strauch, K. (Konstantin), Li, Y. (Yunmin), Jansen, J.R.C. (Jos), Visscher, P.M. (Peter M.), Knight, J.C. (Julian), Psaty, B.M. (Bruce), Ripatti, S. (Samuli), Teumer, A. (Alexander), Frayling, T.M. (Timothy), Metspalu, A. (Andres), Meurs, J.B.J. (Joyce) van, Franke, L. (Lude), Westra, H.J. (Harm-Jan), Peters, M.J. (Marjolein), Esko, T. (Tõnu), Yaghootkar, H. (Hanieh), Schurmann, C. (Claudia), Kettunen, J. (Johannes), Christiansen, M.W. (Mark), Fairfax, B.P. (Benjamin), Schramm, K. (Katharina), Powell, J.E. (Joseph), Zhernakova, A. (Alexandra), Veldink, J.H. (Jan), Berg, L.H. (Leonard) van den, Karjalainen, J. (Juha), Withoff, S. (Sebo), Uitterlinden, A.G. (André), Hofman, B., Rivadeneira Ramirez, F. (Fernando), Hoen, P.A.C. (Peter) 't, Reinmaa, E. (Eva), Fischer, K. (Kathelijn), Nelis, M. (Mari), Milani, A.L. (Alfredo), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A.B. (Andrew), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Homuth, G. (Georg), Nauck, M.A. (Matthias), Radke, D. (Dörte), Vol̈ker, U. (Uwe), Perola, M. (Markus), Salomaa, V. (Veikko), Brody, J.A. (Jennifer A.), Suchy-Dicey, A. (Astrid), Gharib, S.A. (Sina), Enquobahrie, D., Lumley, T. (Thomas), Montgomery, G.W., Makino, S. (Seiko), Prokisch, H. (Holger), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Meitinger, T. (Thomas), Strauch, K. (Konstantin), Li, Y. (Yunmin), Jansen, J.R.C. (Jos), Visscher, P.M. (Peter M.), Knight, J.C. (Julian), Psaty, B.M. (Bruce), Ripatti, S. (Samuli), Teumer, A. (Alexander), Frayling, T.M. (Timothy), Metspalu, A. (Andres), Meurs, J.B.J. (Joyce) van, and Franke, L. (Lude)
Abstract: Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3′ UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
Published: 2013
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20. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

Author: Yaghootkar, H. (Hanieh), Lamina, C. (Claudia), Scott, R.A. (Robert), Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Warren, L.L. (Liling), Stancáková, A. (Alena), Buxbaum, S.G. (Sarah), Lyytikäinen, L.-P. (Leo-Pekka), Henneman, P. (Peter), Wu, Y. (Ying), Cheung, C.Y.Y. (Chloe), Pankow, J.S. (James), Jackson, A.U. (Anne), Gustafsson, S. (Stefan), Zhao, J.H. (Jing Hua), Ballantyne, C. (Christie), Xie, W. (Weijia), Bergman, R.N. (Richard), Boehnke, M. (Michael), El Bouazzaoui, F. (Fatiha), Collins, F.S. (Francis), Dunn, S.H. (Sandra), Dupuis, J. (Josée), Forouhi, N.G. (Nita), Gillson, C.J. (Christopher), Hattersley, A.T. (Andrew), Hong, J. (Jaeyoung), Kähönen, M. (Mika), Kuusisto, J. (Johanna), Kedenko, L. (Lyudmyla), Kronenberg, F. (Florian), Doria, A. (Andrea), Assimes, T.L. (Themistocles), Ferrannini, E. (Ele), Hansen, T. (Torben), Hao, K. (Ke), Häring, H. (Hans), Knowles, J.W. (Joshua), Lindgren, C.M. (Cecilia), Nolan, J.J. (John), Paananen, J. (Jussi), Pedersen, O. (Oluf), Quertermous, T. (Thomas), Smith, U. (Ulf), Lehtimäki, T. (Terho), Liu, C.-T. (Ching-Ti), Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Morris, A.D. (Andrew), Vasan, R.S. (Ramachandran Srini), Spector, T.D. (Timothy), Teslovich, T.M. (Tanya), Tuomilehto, J. (Jaakko), Willems van Dijk, J.A.P. (Ko), Viikari, J. (Jorma), Zhu, N. (Na), Langenberg, C. (Claudia), Ingelsson, E. (Erik), Semple, R.K. (Robert), Sinaiko, A. (Alan), Palmer, C.N.A. (Colin), Walker, M. (Mark), Lam, K.S.L. (Karen), Paulweber, B. (Bernhard), Mohlke, K.L. (Karen), Duijn, C.M. (Cornelia) van, Raitakari, O. (Olli), Bidulescu, A. (Aurelian), Wareham, N.J. (Nick), Laakso, M. (Markku), Waterworth, D. (Dawn), Lawlor, D.A. (Debbie), Meigs, J.B. (James), Richards, J.B. (Brent), Frayling, T.M. (Timothy), Yaghootkar, H. (Hanieh), Lamina, C. (Claudia), Scott, R.A. (Robert), Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Warren, L.L. (Liling), Stancáková, A. (Alena), Buxbaum, S.G. (Sarah), Lyytikäinen, L.-P. (Leo-Pekka), Henneman, P. (Peter), Wu, Y. (Ying), Cheung, C.Y.Y. (Chloe), Pankow, J.S. (James), Jackson, A.U. (Anne), Gustafsson, S. (Stefan), Zhao, J.H. (Jing Hua), Ballantyne, C. (Christie), Xie, W. (Weijia), Bergman, R.N. (Richard), Boehnke, M. (Michael), El Bouazzaoui, F. (Fatiha), Collins, F.S. (Francis), Dunn, S.H. (Sandra), Dupuis, J. (Josée), Forouhi, N.G. (Nita), Gillson, C.J. (Christopher), Hattersley, A.T. (Andrew), Hong, J. (Jaeyoung), Kähönen, M. (Mika), Kuusisto, J. (Johanna), Kedenko, L. (Lyudmyla), Kronenberg, F. (Florian), Doria, A. (Andrea), Assimes, T.L. (Themistocles), Ferrannini, E. (Ele), Hansen, T. (Torben), Hao, K. (Ke), Häring, H. (Hans), Knowles, J.W. (Joshua), Lindgren, C.M. (Cecilia), Nolan, J.J. (John), Paananen, J. (Jussi), Pedersen, O. (Oluf), Quertermous, T. (Thomas), Smith, U. (Ulf), Lehtimäki, T. (Terho), Liu, C.-T. (Ching-Ti), Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Morris, A.D. (Andrew), Vasan, R.S. (Ramachandran Srini), Spector, T.D. (Timothy), Teslovich, T.M. (Tanya), Tuomilehto, J. (Jaakko), Willems van Dijk, J.A.P. (Ko), Viikari, J. (Jorma), Zhu, N. (Na), Langenberg, C. (Claudia), Ingelsson, E. (Erik), Semple, R.K. (Robert), Sinaiko, A. (Alan), Palmer, C.N.A. (Colin), Walker, M. (Mark), Lam, K.S.L. (Karen), Paulweber, B. (Bernhard), Mohlke, K.L. (Karen), Duijn, C.M. (Cornelia) van, Raitakari, O. (Olli), Bidulescu, A. (Aurelian), Wareham, N.J. (Nick), Laakso, M. (Markku), Waterworth, D. (Dawn), Lawlor, D.A. (Debbie), Meigs, J.B. (James), Richards, J.B. (Brent), and Frayling, T.M. (Timothy)
Abstract: Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to te
Published: 2013
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21. 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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21 results on '"Yaghootkar, H. (Hanieh)"'

1. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

2. Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits

3. Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

4. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

5. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

6. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

7. Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

8. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

9. Rare and low-frequency coding variants alter human adult height

10. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

11. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

12. Genome-wide associations for birth weight and correlations with adult disease

13. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

14. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

15. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

16. Cell Specific eQTL Analysis without Sorting Cells

17. The transcriptional landscape of age in human peripheral blood

18. A Genetic variant in the seed region of miR-4513 shows pleiotropic effects on lipid and glucose homeostasis, blood pressure, and coronary artery disease

19. Systematic identification of trans eQTLs as putative drivers of known disease associations

20. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

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

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21 results on '"Yaghootkar, H. (Hanieh)"'

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