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

Momoko Horikoshi; Robin N Beaumont; Felix R Day; Nicole M Warrington; Marjolein N Kooijman; Juan Fernandez-Tajes; Bjarke Feenstra; Natalie R van Zuydam; Kyle J Gaulton; Niels Grarup; Jonathan P Bradfield; David P Strachan; Ruifang Li-Gao; Tarunveer S Ahluwalia; Eskil Kreiner; Rico Rueedi; Leo-Pekka Lyytikäinen; Diana L Cousminer; Ying Wu; Elisabeth Thiering; Carol A Wang; Christian T Have; Jouke-Jan Hottenga; Natalia Vilor-Tejedor; Peter K Joshi; Eileen Tai Hui Boh; Ioanna Ntalla; Niina Pitkänen; Anubha Mahajan; Elisabeth M van Leeuwen; Raimo Joro; Vasiliki Lagou; Michael Nodzenski; Louise A Diver; Krina T Zondervan; Mariona Bustamante; Pedro Marques-Vidal; Josep M Mercader; Amanda J Bennett; Nilufer Rahmioglu; Dale R Nyholt; Ronald Ching Wan Ma; Claudia Ha Ting Tam; Wing Hung Tam; Santhi K Ganesh; Frank Ja van Rooij; Samuel E Jones; Po-Ru Loh; Katherine S Ruth; Marcus A Tuke; Jessica Tyrrell; Andrew R Wood; Hanieh Yaghootkar; Denise M Scholtens; Lavinia Paternoster; Inga Prokopenko; Peter Kovacs; Mustafa Atalay; Sara M Willems; Kalliope Panoutsopoulou; Xu Wang; Lisbeth Carstensen; Frank Geller; Katharina E Schraut; Mario Murcia; Catharina Em van Beijsterveldt; Gonneke Willemsen; Emil V R Appel; Cilius E Fonvig; Caecilie Trier; Carla Mt Tiesler; Marie Standl; Zoltán Kutalik; Sílvia Bonas-Guarch; David M Hougaard; Friman Sánchez; David Torrents; Johannes Waage; Mads V Hollegaard; Hugoline G de Haan; Frits R Rosendaal; Carolina Medina-Gomez; Susan M Ring; Gibran Hemani; George McMahon; Neil R Robertson; Christopher J Groves; Claudia Langenberg; Jian'an Luan; Robert A Scott; Jing Hua Zhao; Frank D Mentch; Scott M MacKenzie; Rebecca M Reynolds; William L Lowe, Jr; Anke Tönjes; Michael Stumvoll; Virpi Lindi; Timo A Lakka; Cornelia M van Duijn; CHARGE Consortium Hematology Working Group

doi:10.1038/nature19806

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

Journal article

Peer reviewed

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

Momoko Horikoshi, Robin N Beaumont, Felix R Day, Nicole M Warrington, Marjolein N Kooijman, Juan Fernandez-Tajes, Bjarke Feenstra, Natalie R van Zuydam, Kyle J Gaulton, Niels Grarup, …

Nature (London), Vol.538(7624), pp.248-252

13/10/2016

DOI: https://doi.org/10.1038/nature19806

PMID: 27680694

Abstract

Adult

Aging - genetics

Anthropometry

Birth Weight - genetics

Blood Pressure - genetics

Chromatin Assembly and Disassembly

Cohort Studies

Coronary Artery Disease - genetics

Datasets as Topic

Diabetes Mellitus, Type 2 - genetics

Female

Fetus - metabolism

Genetic Loci - genetics

Genetic Predisposition to Disease

Genetic Variation - genetics

Genome-Wide Association Study

Genomic Imprinting - genetics

Genotype

Glucose - metabolism

Glycogen - biosynthesis

Humans

Insulin - metabolism

Male

Phenotype

Signal Transduction

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 ). 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 (R = -0.22, P = 5.5 × 10 ), T2D (R = -0.27, P = 1.1 × 10 ) and coronary artery disease (R = -0.30, P = 6.5 × 10 ). 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 ). 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.

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Title: Genome-wide associations for birth weight and correlations with adult disease
Creators: Momoko Horikoshi - Oxford Centre for Diabetes, Endocrinology and Metabolism
Robin N Beaumont - University of Exeter
Felix R Day - University of Cambridge
Nicole M Warrington - University of Queensland
Marjolein N Kooijman - Erasmus MC
Juan Fernandez-Tajes - University of Oxford
Bjarke Feenstra - Statens Serum Institut
Natalie R van Zuydam - University of Oxford
Kyle J Gaulton - University of California, San Diego
Niels Grarup - University of Copenhagen
Jonathan P Bradfield - Children's Hospital of Philadelphia
David P Strachan - St George's, University of London
Ruifang Li-Gao - Leiden University Medical Center
Tarunveer S Ahluwalia - University of Copenhagen
Eskil Kreiner - Copenhagen Prospective Studies on Asthma in Childhood
Rico Rueedi - SIB Swiss Institute of Bioinformatics
Leo-Pekka Lyytikäinen - University of Tampere
Diana L Cousminer - University of Pennsylvania
Ying Wu - Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
Elisabeth Thiering - Helmholtz Zentrum München
Carol A Wang - University of Western Australia
Christian T Have - University of Copenhagen
Jouke-Jan Hottenga - University of Amsterdam
Natalia Vilor-Tejedor - CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
Peter K Joshi - University of Edinburgh
Eileen Tai Hui Boh - National University of Singapore
Ioanna Ntalla - Harokopio University of Athens
Niina Pitkänen - University of Turku
Anubha Mahajan - University of Oxford
Elisabeth M van Leeuwen - Erasmus MC
Raimo Joro - University of Eastern Finland
Vasiliki Lagou - KU Leuven
Michael Nodzenski - Northwestern University
Louise A Diver - University of Glasgow
Krina T Zondervan - University of Oxford
Mariona Bustamante - Barcelona Institute for Global Health
Pedro Marques-Vidal - Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Josep M Mercader - Universitat Politècnica de Catalunya
Amanda J Bennett - University of Oxford
Nilufer Rahmioglu - Wellcome Centre for Human Genetics
Dale R Nyholt - Queensland University of Technology
Ronald Ching Wan Ma - Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
Claudia Ha Ting Tam - Chinese University of Hong Kong
Wing Hung Tam - Chinese University of Hong Kong
Santhi K Ganesh - Michigan Medicine
Frank Ja van Rooij - Erasmus MC
Samuel E Jones - University of Exeter
Po-Ru Loh - Broad Institute
Katherine S Ruth - University of Exeter
Marcus A Tuke - University of Exeter
Jessica Tyrrell - University of Exeter
Andrew R Wood - University of Exeter
Hanieh Yaghootkar - University of Exeter
Denise M Scholtens - Northwestern University
Lavinia Paternoster - University of Bristol
Inga Prokopenko - Genomics
Peter Kovacs - IFB Adiposity Diseases
Mustafa Atalay - University of Eastern Finland
Sara M Willems - Erasmus MC
Kalliope Panoutsopoulou - Wellcome Sanger Institute
Xu Wang - National University of Singapore
Lisbeth Carstensen - Statens Serum Institut
Frank Geller - Statens Serum Institut
Katharina E Schraut - University of Edinburgh
Mario Murcia - Universitat Jaume I
Catharina Em van Beijsterveldt - University of Amsterdam
Gonneke Willemsen - University of Amsterdam
Emil V R Appel - University of Copenhagen
Cilius E Fonvig - Holbæk Sygehus
Caecilie Trier - Copenhagen University Hospital
Carla Mt Tiesler - Helmholtz Zentrum München
Marie Standl - Helmholtz Zentrum München
Zoltán Kutalik - SIB Swiss Institute of Bioinformatics
Sílvia Bonas-Guarch - Barcelona Supercomputing Center
David M Hougaard - Statens Serum Institut
Friman Sánchez - Barcelona Supercomputing Center
David Torrents - Institució Catalana de Recerca i Estudis Avançats
Johannes Waage - University of Copenhagen
Mads V Hollegaard - Statens Serum Institut
Hugoline G de Haan - Leiden University Medical Center
Frits R Rosendaal - Leiden University Medical Center
Carolina Medina-Gomez - Erasmus MC
Susan M Ring - University of Bristol
Gibran Hemani - University of Bristol
George McMahon - University of Bristol
Neil R Robertson - University of Oxford
Christopher J Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Claudia Langenberg - University of Cambridge
Jian'an Luan - University of Cambridge
Robert A Scott - University of Cambridge
Jing Hua Zhao - University of Cambridge
Frank D Mentch - Children's Hospital of Philadelphia
Scott M MacKenzie - University of Glasgow
Rebecca M Reynolds - The Queen's Medical Research Institute
William L Lowe, Jr - Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, USA
Anke Tönjes - Leipzig University
Michael Stumvoll - Leipzig University
Virpi Lindi - University of Eastern Finland
Timo A Lakka - University of Eastern Finland
Cornelia M van Duijn - Erasmus MC
CHARGE Consortium Hematology Working Group
Publication Details: Nature (London), Vol.538(7624), pp.248-252
Date published: 13/10/2016
Grant note: R01 HD056465 / NICHD NIH HHS MC_UU_12013/1 / Medical Research Council MR/J012165/1 / Medical Research Council MC_QA137853 / Medical Research Council CZB/4/733 / Chief Scientist Office G0500070 / Medical Research Council 202802/Z/16/Z / Wellcome Trust MC_U106179471 / Medical Research Council MC_PC_15018 / Medical Research Council G9815508 / Medical Research Council
Identifiers: 99928827502346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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