Journal
HUMAN MOLECULAR GENETICS
Volume 31, Issue 11, Pages 1762-1775Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddab356
Keywords
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Funding
- US National Institutes of Health [R01 DK10324]
- European Research Council under the European Union [669545]
- British Heart Foundation [CS/16/4/32482, AA/18/7/34219]
- NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust
- University of Bristol
- UK Medical Research Council (MRC) [MC_UU_00011/6]
- Wellcome Trust [217065/Z/19/Z, WT088806, WT101597MA]
- 23andMe
- UK Economic and Social Science Research Council (ESRC) [MR/N024397/1]
- National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber and the Clinical Research Network (CRN)
- South West NHS Research and Development, Exeter NHS Research and Development
- Darlington Trust
- Peninsula National Institute of Health Research Clinical Research Facility at the University of Exeter
- Royal Society [104150/Z/14/Z]
- GW4 BIOMED DTP from the UK Medical Research Council (MRC)
- UK MRC Skills Development Fellowship [MR/P014054/1]
- UK MRC Vice -Chancellor's Fellowship
- Royal Society Sir Henry Dale Fellowship [104150/Z/14/Z]
- British Heart Foundation Chair [CH/F/20/90003]
- NIHR [NF -061610102]
- NIHR Senior Investigator award
- Wellcome Trust Senior Investigator award [098395/Z/12/Z]
- Innovative Medicines Initiative 2 as part of the 'Stratification of obese phenotypes to optimize future obesity therapy (SOPHIA) Joint Undertaking [875534]
- European Union's Horizon 2020 research and innovation programme
- EFPIA
- T1D Exchange
- JDRF, an Obesity Action Coalition'
- Australian National Health and Medical Research Council [APP1137714]
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Recent studies have shown that higher birthweight is associated with higher adult body mass index (BMI). Alleles predisposing to greater adult adiposity may affect fetal growth and birthweight. Fetal genetic predisposition to higher metabolically favorable adiposity and BMI is associated with birthweight, with the former showing a dose-dependent association while the latter does not.
Background Higher birthweight is associated with higher adult body mass index (BMI). Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favorable adiposity alleles on birthweight is unknown. Aim We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favorable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI. Methods We used published genome wide association study data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favorable adult adiposity or BMI. We combined summary data across single nucleotide polymorphisms (SNPs) with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association. Results Fetal genetic predisposition to higher metabolically favorable adult adiposity and higher adult BMI were both associated with higher birthweight (3 g per effect allele (95% CI: 1-5) averaged over 14 SNPs; P = 0.002; 0.5 g per effect allele (95% CI: 0-1) averaged over 76 SNPs; P = 0.042, respectively). SNPs with greater effects on metabolically favorable adiposity tended to have greater effects on birthweight (R-2 = 0.2912, P = 0.027). There was no dose-dependent association for BMI (R-2 = -0.0019, P = 0.602). Conclusions Fetal genetic predisposition to both higher adult metabolically favorable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favorable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not.
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