PT - JOURNAL ARTICLE AU - Robin N Beaumont AU - Nicole M Warrington AU - Alana Cavadino AU - Jessica Tyrrell AU - Michael Nodzenski AU - Momoko Horikoshi AU - Frank Geller AU - Ronny Myhre AU - Rebecca C. Richmond AU - Lavinia Paternoster AU - Jonathan P. Bradfield AU - Eskil Kreiner-Møller AU - Ville Huikari AU - Sarah Metrustry AU - Kathryn L. Lunetta AU - Jodie N. Painter AU - Jouke-Jan Hottenga AU - Catherine Allard AU - Sheila J. Barton AU - Ana Espinosa AU - Julie A. Marsh AU - Catherine Potter AU - Ge Zhang AU - Wei Ang AU - Diane J. Berry AU - Luigi Bouchard AU - Shikta Das AU - Early Growth Genetics (EGG) Consortium AU - Hakon Hakonarson AU - Jani Heikkinen AU - Øyvind Helgeland AU - Berthold Hocher AU - Albert Hofman AU - Hazel M. Inskip AU - Samuel E Jones AU - Manolis Kogevinas AU - Penelope A. Lind AU - Letizia Marullo AU - Sarah E. Medland AU - Anna Murray AU - Jeffrey C. Murray AU - Pål R. Njølstad AU - Ellen A. Nohr AU - Christoph Reichetzeder AU - Susan M. Ring AU - Katherine S Ruth AU - Loreto Santa-Marina AU - Denise M. Scholtens AU - Sylvain Sebert AU - Verena Sengpiel AU - Marcus A Tuke AU - Marc Vaudel AU - Michael N Weedon AU - Gonneke Willemsen AU - Andrew R Wood AU - Hanieh Yaghootkar AU - Louis J. Muglia AU - Meike Bartels AU - Caroline L. Relton AU - Craig E. Pennell AU - Leda Chatzi AU - Xavier Estivill AU - John W. Holloway AU - Dorret I. Boomsma AU - Grant W. Montgomery AU - Joanne M. Murabito AU - Tim D. Spector AU - Christine Power AU - Marjo-Ritta Järvelin AU - Hans Bisgaard AU - Struan F.A. Grant AU - Thorkild I.A. Sørensen AU - Vincent W. Jaddoe AU - Bo Jacobsson AU - Mads Melbye AU - Mark I. McCarthy AU - Andrew T. Hattersley AU - M. Geoffrey Hayes AU - Timothy M. Frayling AU - Marie-France Hivert AU - Janine F. Felix AU - Elina Hyppönen AU - William L. Lowe, Jr. AU - David M Evans AU - Debbie A. Lawlor AU - Bjarke Feenstra AU - Rachel M. Freathy TI - Genome-wide association study of offspring birth weight in 86,577 women highlights maternal genetic effects that are independent of fetal genetics AID - 10.1101/034207 DP - 2017 Jan 01 TA - bioRxiv PG - 034207 4099 - http://biorxiv.org/content/early/2017/09/08/034207.short 4100 - http://biorxiv.org/content/early/2017/09/08/034207.full AB - Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about how maternal genetic variation influences fetal growth. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth.We meta-analysed GWAS 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 and CYP3A7) showed evidence of association with offspring birth weight at P<5x10-8. The SEM analyses showed 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 effects of maternal glucose, cytochrome P450 activity and gestational duration, and potential effects of maternal blood pressure and immune function on fetal growth. Further characterization of these associations, for example 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.