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Genetic evidence for causal relationships between maternal obesity-related traits and birth weight

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dc.contributor.authorTyrrell, J.
dc.contributor.authorRichmond, R.
dc.contributor.authorPalmer, T.
dc.contributor.authorFeenstra, B.
dc.contributor.authorRangarajan, J.
dc.contributor.authorMetrustry, S.
dc.contributor.authorCavadino, A.
dc.contributor.authorPaternoster, L.
dc.contributor.authorArmstrong, L.
dc.contributor.authorDe Silva, N.
dc.contributor.authorWood, A.
dc.contributor.authorHorikoshi, M.
dc.contributor.authorGeller, F.
dc.contributor.authorMyhre, R.
dc.contributor.authorBradfield, J.
dc.contributor.authorKreiner-Møller, E.
dc.contributor.authorHuikari, I.
dc.contributor.authorPainter, J.
dc.contributor.authorHottenga, J.
dc.contributor.authorAllard, C.
dc.contributor.authoret al.
dc.date.issued2016
dc.descriptionData source: Supplemental Content, http://jama.jamanetwork.com/article.aspx?articleid=2503173&utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jama.2016.1975#tab12
dc.description.abstractNeonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1×10(-5)), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
dc.identifier.citationJournal of the American Medical Association (JAMA), 2016; 315(11):1129-1140
dc.identifier.doi10.1001/jama.2016.1975
dc.identifier.issn0098-7484
dc.identifier.issn1538-3598
dc.identifier.orcidLawlor, D. [0000-0002-6793-2262]
dc.identifier.urihttps://hdl.handle.net/11541.2/118815
dc.language.isoen
dc.publisherAMER MEDICAL ASSOC
dc.relation.fundingEuropean Research Council 323195SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC
dc.relation.fundingWellcome Trust
dc.relation.fundingNational Institutes of Health Research
dc.relation.fundingARC
dc.rightsCopyright 2016 American Medical Association Access Condition Notes: Available after 15 September 2016
dc.source.urihttps://doi.org/10.1001/jama.2016.1975
dc.subjectEarly Growth Genetics (EGG) Consortium
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectObesity
dc.subjectBirth Weight
dc.subjectBlood Glucose
dc.subjectTriglycerides
dc.subjectBody Mass Index
dc.subjectFasting
dc.subjectPregnancy
dc.subjectBlood Pressure
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectInfant, Newborn
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectMendelian Randomization Analysis
dc.titleGenetic evidence for causal relationships between maternal obesity-related traits and birth weight
dc.typeJournal article
pubs.publication-statusPublished
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ror.mmsid9916056172801831

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