Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

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dc.contributor.authorFreathy, R.
dc.contributor.authorMook-Kanamori, D.
dc.contributor.authorSovio, U.
dc.contributor.authorProkopenko, I.
dc.contributor.authorTimpson, N.
dc.contributor.authorBerry, D.
dc.contributor.authorWarrington, N.
dc.contributor.authorWiden, E.
dc.contributor.authorJan Hottenga, J.
dc.contributor.authorKaakinen, M.
dc.contributor.authorLange, L.
dc.contributor.authorBradfield, J.
dc.contributor.authorKerkhof, M.
dc.contributor.authorMarsh, J.
dc.contributor.authorMägi, R.
dc.contributor.authorChen, C.-M.
dc.contributor.authorLyon, H.
dc.contributor.authorKirin, M.
dc.contributor.authorAdair, L.
dc.contributor.authorAulchenko, Y.
dc.contributor.authoret al.
dc.date.issued2010
dc.description.abstractTo identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 × 10−35) and rs9883204 in ADCY5 (P = 7 × 10−15) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes1, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes2, 3 has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight–lowering alleles were, on average, 113 g (95% CI 89–137 g) lighter at birth than the 24% with zero or one alleles (Ptrend = 7 × 10−30). The impact on birth weight is similar to that of a mother smoking 4–5 cigarettes per day in the third trimester of pregnancy.
dc.description.statementofresponsibilityRachel M Freathy ... The Genetic Investigation of ANthropometric Traits (GIANT) Consortium ... The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) ...The Wellcome Trust Case Control Consortium (WTCCC) ... Lyle J Palmer ... et al. for the Early Growth Genetics (EGG) Consortium.
dc.identifier.citationNature Genetics, 2010; 42(5):430-435
dc.identifier.doi10.1038/ng.567
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.urihttp://hdl.handle.net/2440/88791
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/572613
dc.rights© 2010 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/ng.567
dc.subjectGenetic Investigation of ANthropometric Traits (GIANT) Consortium
dc.subjectMeta-Analyses of Glucose and Insulin-related traits Consortium
dc.subjectWellcome Trust Case Control Consortium
dc.subjectEarly Growth Genetics (EGG) Consortium
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectGenetic Predisposition to Disease
dc.subjectBirth Weight
dc.subjectIsoenzymes
dc.subjectGlucose
dc.subjectCyclins
dc.subjectCohort Studies
dc.subjectPregnancy
dc.subjectGenotype
dc.subjectAlleles
dc.subjectModels, Genetic
dc.subjectFemale
dc.subjectMale
dc.subjectAdenylyl Cyclases
dc.subjectEthnicity
dc.titleVariants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
dc.typeJournal article
pubs.publication-statusPublished

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