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

Horikoshi M, Robin N. Beaumont, Felix R. Day, Warrington NM, Kooijman MN, Fernandez-Tajes J, Feenstra B, Van Zuydam NR, Gaulton KJ, Grarup N, Bradfield JP, Strachan DP, Li-Gao R, Ahluwalia TS, Kreiner E, Rueedi R, Lyytikäinen LP, Cousminer DL, Wu Y, Thiering E, Wang CA, Have CT, Jouke-Jan Hottenga, Vilor-Tejedor N, Joshi PK, Boh ETH, Ntalla I, Pitkänen N, Anubha Mahajan, van Leeuwen EM, Joro R, Lagou V, Nodzenski M, Diver LA, Krina T. Zondervan, Bustamante M, Marques-Vidal P, Mercader JM, Bennett AJ, Nilüfer Rahmioğlu, Dale R. Nyholt, Ma RCW, Tam CHT, Tam WH, Ganesh SK, van Rooij FJ, Samuel E. Jones, Loh PR, Ruth KS, Tuke MA, Jessica Tyrrell, Andrew R. Wood, Hanieh Yaghootkar, Scholtens DM, Paternoster L, Inga Prokopenko, Kovacs P, Atalay M, Willems SM, Panoutsopoulou K, Wang X, Carstensen L, Geller F, Schraut KE, Murcia M, van Beijsterveldt CE, Gonneke Willemsen, Appel EVR, Fonvig CE, Trier C, Tiesler CM, Standl M, Kutalik Z, Bonas-Guarch S, Hougaard DM, Sánchez F, Torrents D, Waage J, Hollegaard MV, de Haan HG, Rosendaal FR, Carolina Medina-Gomez, Ring SM, Gibran Hemani, McMahon G, Robertson NR, Groves CJ, Claudia Langenberg, Luan J, Scott RA, Zhao JH, Mentch FD, MacKenzie SM, Reynolds RM, Lowe WL Jr, Tönjes A, Stumvoll M, Lindi V, Lakka TA, van Duijn CM, Kiess W, Körner A, Sørensen TI, Niinikoski H, Pahkala K, Raitakari OT, Zeggini E, Dedoussis GV, Teo YY, Saw SM, Melbye M, Campbell H, Wilson JF, Vrijheid M, de Geus EJC, Boomsma DI, Kadarmideen HN, Holm JC, Sylvain Sebért, Sebert S, Hattersley AT, Beilin LJ, Newnham JP, Pennell CE, Heinrich J, Adair LS, Borja JB, Mohlke KL, Eriksson JG, Widen E, Kähönen M, Viikari JS, Lehtimäki T, Vollenweider P, Bønnelykke K, Bisgaard H, Mook-Kanamori DO, Hofman A, Fernando Rivadeneira, André G Uitterlinden, Pisinger C, Pedersen O, Power C, Elina Hyppӧnen, Wareham NJ, Håkon Håkonarson, Davies E, Walker BR, Jaddoe VW, Jarvelin MR, Grant SFA, Vaag A, Debbie A. Lawlor, George Davey Smith, Timothy M. Frayling, Davey Smith G, Andrew P. Morris, Ong KK, Felix JF, Nicholas J Timpson, Perry JR, Evans DM, Mark I. McCarthy, Rachel M. Freathy, Freathy RM
OA: closed
📄 Open PDF View on PubMed View at publisher

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.

My notes (saved in your browser only)

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

Source provenance

europepmc
last seen: 2026-08-13T06:15:24.848197+00:00