Journal article
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
Nature genetics, Vol.51(5), pp.804-814
05/01/2019
DOI: 10.1038/s41588-019-0403-1
PMCID: PMC6522365
PMID: 31043758
Abstract
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Details
- Title: Subtitle
- Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
- Creators
- Nicole M Warrington - The University of QueenslandRobin N Beaumont - Royal Devon and Exeter HospitalMomoko Horikoshi - University of OxfordFelix R Day - MRC Epidemiology UnitØyvind Helgeland - Haukeland University HospitalCharles Laurin - Medical Research CouncilJonas Bacelis - Sahlgrenska University HospitalShouneng Peng - Icahn School of Medicine at Mount SinaiKe Hao - Icahn School of Medicine at Mount SinaiBjarke Feenstra - Statens Serum InstitutAndrew R Wood - University of ExeterAnubha Mahajan - Centre for Human GeneticsJessica Tyrrell - Royal Devon and Exeter HospitalNeil R Robertson - Centre for Human GeneticsN William Rayner - Centre for Human GeneticsZhen Qiao - The University of QueenslandGunn-Helen Moen - Oslo University HospitalMarc Vaudel - University of BergenCarmen J Marsit - Emory UniversityJia Chen - Icahn School of Medicine at Mount SinaiMichael Nodzenski - Northwestern UniversityTheresia M Schnurr - Novo Nordisk FoundationMohammad H Zafarmand - Amsterdam UMC Location University of AmsterdamJonathan P Bradfield - Children's Hospital of PhiladelphiaNiels Grarup - Novo Nordisk FoundationMarjolein N Kooijman - Erasmus MCRuifang Li-Gao - Leiden University Medical CenterFrank Geller - Statens Serum InstitutTarunveer S Ahluwalia - University of CopenhagenLavinia Paternoster - Medical Research CouncilRico Rueedi - University of LausanneVille Huikari - University of OuluJouke-Jan Hottenga - Amsterdam Public HealthLeo-Pekka Lyytikäinen - University of TampereAlana Cavadino - Great Ormond Street HospitalSarah Metrustry - King's College LondonDiana L Cousminer - Children's Hospital of PhiladelphiaYing Wu - University of North Carolina at Chapel HillElisabeth Thiering - Helmholtz Zentrum MünchenCarol A Wang - University of Newcastle AustraliaChristian T Have - University of CopenhagenNatalia Vilor-Tejedor - Barcelonaβeta Brain Research CenterPeter K Joshi - University of EdinburghJodie N Painter - QIMR Berghofer Medical Research InstituteIoanna Ntalla - Queen Mary University of LondonRonny Myhre - Norwegian Institute of Public HealthNiina Pitkänen - University of TurkuElisabeth M van Leeuwen - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the NetherlandsRaimo Joro - University of Eastern FinlandVasiliki Lagou - KU LeuvenRebecca C Richmond - Medical Research CouncilAna Espinosa - Barcelona Institute for Global HealthSheila J Barton - MRC Lifecourse Epidemiology UnitHazel M Inskip - MRC Lifecourse Epidemiology UnitJohn W Holloway - University of SouthamptonLoreto Santa-Marina - Biogipuzkoa Health Research InstituteXavier Estivill - Hospital Universitario DexeusWei Ang - The University of Western AustraliaJulie A Marsh - The University of Western AustraliaChristoph Reichetzeder - University of PotsdamLetizia Marullo - University of FerraraBerthold Hocher - Reproductive & Genetic Hospital CITIC-XiangyaKathryn L Lunetta - Boston UniversityJoanne M Murabito - Boston UniversityCaroline L Relton - University of BristolManolis Kogevinas - Barcelona Institute for Global HealthLeda Chatzi - University of Southern CaliforniaCatherine Allard - Centre Hospitalier Universitaire de SherbrookeLuigi Bouchard - Centre Hospitalier Universitaire de SherbrookeMarie-France Hivert - Université de SherbrookeGe Zhang - Cincinnati Children's Hospital Medical CenterLouis J Muglia - Cincinnati Children's Hospital Medical CenterJani Heikkinen - Finland UniversityCamilla S Morgen - University of CopenhagenAntoine H C van Kampen - University of AmsterdamBarbera D C van Schaik - Amsterdam UMC Location University of AmsterdamFrank D Mentch - Children's Hospital of PhiladelphiaClaudia Langenberg - MRC Epidemiology UnitJian'an Luan - University of CambridgeRobert A Scott - University of CambridgeJing Hua Zhao - University of CambridgeGibran Hemani - University of BristolSusan M Ring - Medical Research CouncilAmanda J Bennett - Oxford Centre for Diabetes, Endocrinology and MetabolismKyle J Gaulton - Centre for Human GeneticsJuan Fernandez-Tajes - Centre for Human GeneticsNatalie R van Zuydam - Centre for Human GeneticsCarolina Medina-Gomez - Erasmus MCHugoline G de Haan - Leiden University Medical CenterFrits R Rosendaal - Leiden University Medical CenterZoltán Kutalik - Institute of Social and Preventive MedicinePedro Marques-Vidal - University of LausanneShikta Das - MRC Unit for Lifelong Health and AgeingGonneke Willemsen - Vrije Universiteit AmsterdamHamdi Mbarek - GGD AmsterdamMartina Müller-Nurasyid - Helmholtz Zentrum MünchenMarie Standl - Helmholtz Zentrum MünchenEmil V R Appel - Novo Nordisk FoundationCilius E Fonvig - Copenhagen University HospitalCaecilie Trier - Copenhagen University HospitalEGG ConsortiumJeffrey C Murray (Contributor)
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.51(5), pp.804-814
- DOI
- 10.1038/s41588-019-0403-1
- PMID
- 31043758
- PMCID
- PMC6522365
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 ES029212 / NIEHS NIH HHS MC_UU_12011/4 / Medical Research Council P30 ES023515 / NIEHS NIH HHS MC_UP_A620_1017 / Medical Research Council MC_UU_12013/1 / Medical Research Council MR/J012165/1 / Medical Research Council MC_UU_00011/6 / Medical Research Council 202802/Z/16/Z / Wellcome Trust P30 ES010126 / NIEHS NIH HHS 323195 / European Research Council
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985034981802771
Metrics
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