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

Details

Serval ID
serval:BIB_EDE2E891023A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide associations for birth weight and correlations with adult disease.
Journal
Nature
Author(s)
Horikoshi M., Beaumont R.N., Day F.R., Warrington N.M., Kooijman M.N., Fernandez-Tajes J., Feenstra B., van Zuydam N.R., Gaulton K.J., Grarup N., Bradfield J.P., Strachan D.P., Li-Gao R., Ahluwalia T.S., Kreiner E., Rueedi R., Lyytikäinen L.P., Cousminer D.L., Wu Y., Thiering E., Wang C.A., Have C.T., Hottenga J.J., Vilor-Tejedor N., Joshi P.K., Boh E.T., Ntalla I., Pitkänen N., Mahajan A., van Leeuwen E.M., Joro R., Lagou V., Nodzenski M., Diver L.A., Zondervan K.T., Bustamante M., Marques-Vidal P., Mercader J.M., Bennett A.J., Rahmioglu N., Nyholt D.R., Ma R.C., Tam C.H., Tam W.H., Ganesh S.K., van Rooij F.J., Jones S.E., Loh P.R., Ruth K.S., Tuke M.A., Tyrrell J., Wood A.R., Yaghootkar H., Scholtens D.M., Paternoster L., Prokopenko I., Kovacs P., Atalay M., Willems S.M., Panoutsopoulou K., Wang X., Carstensen L., Geller F., Schraut K.E., Murcia M., van Beijsterveldt C.E., Willemsen G., Appel E.V., Fonvig C.E., Trier C., Tiesler C.M., Standl M., Kutalik Z., Bonàs-Guarch S., Hougaard D.M., Sánchez F., Torrents D., Waage J., Hollegaard M.V., de Haan H.G., Rosendaal F.R., Medina-Gomez C., Ring S.M., Hemani G., McMahon G., Robertson N.R., Groves C.J., Langenberg C., Luan J., Scott R.A., Zhao J.H., Mentch F.D., MacKenzie S.M., Reynolds R.M., Lowe W.L., Tönjes A., Stumvoll M., Lindi V., Lakka T.A., van Duijn C.M., Kiess W., Körner A., Sørensen T.I., Niinikoski H., Pahkala K., Raitakari O.T., Zeggini E., Dedoussis G.V., Teo Y.Y., Saw S.M., Melbye M., Campbell H., Wilson J.F., Vrijheid M., de Geus E.J., Boomsma D.I., Kadarmideen H.N., Holm J.C., Hansen T., Sebert S., Hattersley A.T., Beilin L.J., Newnham J.P., Pennell C.E., Heinrich J., Adair L.S., Borja J.B., Mohlke K.L., Eriksson J.G., Widén E., Kähönen M., Viikari J.S., Lehtimäki T., Vollenweider P., Bønnelykke K., Bisgaard H., Mook-Kanamori D.O., Hofman A., Rivadeneira F., Uitterlinden A.G., Pisinger C., Pedersen O., Power C., Hyppönen E., Wareham N.J., Hakonarson H., Davies E., Walker B.R., Jaddoe V.W., Järvelin M.R., Grant S.F., Vaag A.A., Lawlor D.A., Frayling T.M., Smith G.D., Morris A.P., Ong K.K., Felix J.F., Timpson N.J., Perry J.R., Evans D.M., McCarthy M.I., Freathy R.M.
Working group(s)
CHARGE Consortium Hematology Working Group, Early Growth Genetics (EGG) Consortium
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
28/09/2016
Peer-reviewed
Oui
Volume
538
Number
7624
Pages
248-252
Language
english
Notes
Publication types: JOURNAL ARTICLE

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 disease. These life-course 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.

Pubmed
Create date
02/12/2016 10:02
Last modification date
20/08/2019 17:15
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