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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620039
Title:
Genome-wide associations for birth weight and correlations with adult disease.
Authors:
Horikoshi, Momoko [et al] inc.; .; Hattersley, Andrew T.; Frayling, Timothy M.
Abstract:
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(-8)). 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 (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). 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(-4)). 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.
Citation:
Genome-wide associations for birth weight and correlations with adult disease. 2016, 538 (7624):248-252 Nature
Publisher:
Nature
Journal:
Nature
Issue Date:
28-Sep-2016
URI:
http://hdl.handle.net/11287/620039
DOI:
10.1038/nature19806
PubMed ID:
27680694
Additional Links:
http://dx.doi.org/10.1038/nature19806
Type:
Letter
ISSN:
1476-4687
Appears in Collections:
Diabetes/Endocrine Services; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHorikoshi, Momoko [et al] inc.en
dc.contributor.author.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorFrayling, Timothy M.en
dc.date.accessioned2016-10-19T09:02:16Z-
dc.date.available2016-10-19T09:02:16Z-
dc.date.issued2016-09-28-
dc.identifier.citationGenome-wide associations for birth weight and correlations with adult disease. 2016, 538 (7624):248-252 Natureen
dc.identifier.issn1476-4687-
dc.identifier.pmid27680694-
dc.identifier.doi10.1038/nature19806-
dc.identifier.urihttp://hdl.handle.net/11287/620039-
dc.description.abstractBirth 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(-8)). 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 (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). 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(-4)). 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.en
dc.languageENG-
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/nature19806en
dc.rightsArchived with thanks to Natureen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGenome-wide associations for birth weight and correlations with adult disease.
dc.typeLetteren
dc.identifier.journalNatureen
dc.type.versionIn press (epub ahead of print)en

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