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

Show full item record



Permalink

http://hdl.handle.net/10138/232991

Citation

Beaumont , R N , Warrington , N M , Cavadino , A , Tyrrell , J , Nodzenski , M , Horikoshi , M , Geller , F , Myhre , R , Richmond , R C , Paternoster , L , Bradfield , J P , Kreiner-Møller , E , Huikari , V , Metrustry , S , Lunetta , K L , Painter , J N , Hottenga , J-J , Allard , C , Barton , S J , Espinosa , A , Marsh , J A , Potter , C , Zhang , G , Ang , W , Berry , D J , Bouchard , L , Das , S , Hakonarson , H , Heikkinen , J , Helgeland , Ø , Hocher , B , Hofman , A , Inskip , H M , Jones , S E , Kogevinas , M , Lind , P A , Marullo , L , Medland , S E , Murray , A , Murray , J C , Njølstad , P R , Nohr , E A , Reichetzeder , C , Ring , S M , Ruth , K S , Santa-Marina , L , Scholtens , D M , Sebert , S , Sengpiel , V , Tuke , M A , Vaudel , M , Weedon , M N , Willemsen , G , Wood , A R , Yaghootkar , H , Muglia , L J , Bartels , M , Relton , C L , Pennell , C E , Chatzi , L , Estivill , X , Holloway , J W , Boomsma , D I , Montgomery , G W , Murabito , J M , Spector , T D , Power , C , Järvelin , M-R , Bisgaard , H , Grant , S F A , Sørensen , T I A , Jaddoe , V W , Jacobsson , B , Melbye , M , McCarthy , M I , Hattersley , A T , Hayes , M G , Frayling , T M , Hivert , M-F , Felix , J F , Hyppönen , E , Lowe , W L , Evans , D M , Lawlor , D A , Feenstra , B & and , R M F 2018 , ' 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 ' , Human Molecular Genetics , vol. 27 , no. 4 , pp. 742-756 . https://doi.org/10.1093/hmg/ddx429

Title: 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, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke; and, Rachel M Freathy
Other contributor: University of Helsinki, Institute for Molecular Medicine Finland

Date: 2018-02-15
Language: eng
Number of pages: 15
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
DOI: https://doi.org/10.1093/hmg/ddx429
URI: http://hdl.handle.net/10138/232991
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 x 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.
Subject: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
1182 Biochemistry, cell and molecular biology
GESTATIONAL DIABETES-MELLITUS
FASTING GLUCOSE
BLOOD-PRESSURE
SUSCEPTIBILITY LOCI
HEAD CIRCUMFERENCE
GLUCOKINASE GENE
COMMON VARIANTS
RISK LOCI
METAANALYSIS
DISEASE
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
ddx429.pdf 421.1Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record