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

Author

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

Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Published
2020

2. 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
Full Text
View/download PDF

3. 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
Full Text
View/download PDF

4. 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

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