@article {Feenstra034207, author = {Bjarke Feenstra and Alana Cavadino and Jessica Tyrrell and George McMahon and Michael Nodzenski and Momoko Horikoshi and Frank Geller and Ronny Myhre and Rebecca C. Richmond and Lavinia Paternoster and Jonathan P. Bradfield and Eskil Kreiner-M{\o}ller and Ville Huikari and Sarah Metrustry and Kathryn L. Lunetta and Jodie N. Painter and Jouke-Jan Hottenga and Catherine Allard and Sheila J. Barton and Ana Espinosa and Julie A. Marsh and Catherine Potter and Wei Ang and Diane J. Berry and Luigi Bouchard and Shikta Das and Hakon Hakonarson and Jani Heikkinen and Berthold Hocher and Albert Hofman and Hazel M. Inskip and Manolis Kogevinas and Penelope A. Lind and Letizia Marullo and Sarah E. Medland and Jeffrey C. Murray and Ellen A. Nohr and Christoph Reichetzeder and Susan M. Ring and Loreto Santa-Marina and Denise M. Scholtens and Sylvain Sebert and Verena Sengpiel and Meike Bartels and Caroline L. Relton and Craig E. Pennell and Leda Chatzi and Xavier Estivill and John W. Holloway and Dorret I. Boomsma and Grant W. Montgomery and Joanne M. Murabito and Tim D. Spector and Christine Power and Marjo-Ritta J{\"a}rvelin and Hans Bisgaard and Struan F.A. Grant and Thorkild I.A. S{\o}rensen and Vincent W. Jaddoe and Bo Jacobsson and Mads Melbye and Mark I. McCarthy and Andrew T. Hattersley and M. Geoffrey Hayes and David M. Evans and Marie-France Hivert and Janine F. Felix and Elina Hypp{\"o}nen and William L. Lowe, Jr. and Debbie A. Lawlor and Timothy M. Frayling and Rachel M. Freathy and for the Early Growth Genetics (EGG) Consortium}, title = {Maternal genome-wide association study identifies a fasting glucose variant associated with offspring birth weight}, elocation-id = {034207}, year = {2015}, doi = {10.1101/034207}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Several common fetal genetic variants have been associated with birth weight, but little is known about how maternal genetic variation influences fetal growth through the intra-uterine environment. To identify maternal genetic variants associated with birth weight, we performed a meta-analysis of 11 genome-wide association studies (GWAS; n = 19,626 women of European descent). We selected 18 single nucleotide polymorphisms (SNPs) for replication analysis in up to 13 further studies (n = 18,319 women of European descent). One SNP reached genome-wide significance (rs10830963, P = 2.0 {\texttimes} 10-11) in a combined analysis of discovery and replication results. Rs10830963 is intronic in MTNR1B and is known from previous GWAS to be associated with fasting glucose levels, type 2 diabetes and gestational diabetes. Each copy of rs10830963-G (the allele associated with higher fasting glucose) corresponded to a 31g [95\%CI: 22, 41g] higher offspring birth weight. The association between maternal rs10830963 and birth weight was unaltered by adjustment for any potentially confounding effects of fetal genotype in 8716 maternal-fetal pairs. Although no other SNPs reached genome-wide significance, there was an excess of low P-values among SNPs known to be associated with fasting glucose levels. Our study demonstrates that maternal genetic variation at MTNR1B influences offspring birth weight and supports a broader role of genetic variation affecting maternal glucose levels in fetal growth. Our study also highlights that the effect sizes of associations between other maternal genetic variants and birth weight are unlikely to exceed 20g per allele, and therefore much larger sample sizes will be required to detect them.}, URL = {https://www.biorxiv.org/content/early/2015/12/11/034207}, eprint = {https://www.biorxiv.org/content/early/2015/12/11/034207.full.pdf}, journal = {bioRxiv} }