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Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals

Kilpelainen, Tuomas O., den Hoed, Marcel, Ong, Ken K., Grontved, Anders, Brage, Soren, Jameson, Karen, Cooper, Cyrus, Khaw, Kay-Tee, Ekelund, Ulf, Wareham, Nicholas J. and Loos, Ruth J.F. (2011) Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals American Journal of Clinical Nutrition, 93, (4), pp. 851-860. (doi:10.3945/?ajcn.110.000828). (PMID:21248185 ).

Record type: Article


Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background.

Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight.

Design:A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837).

Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (? ± SE: ?13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (? ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing.

Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

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Published date: April 2011


Local EPrints ID: 181555
ISSN: 0002-9165
PURE UUID: 7e7d5cd3-4abf-49b6-b40a-bbb08d98ad23
ORCID for Cyrus Cooper: ORCID iD

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Date deposited: 14 Apr 2011 11:09
Last modified: 18 Jul 2017 11:59

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Author: Tuomas O. Kilpelainen
Author: Marcel den Hoed
Author: Ken K. Ong
Author: Anders Grontved
Author: Soren Brage
Author: Karen Jameson
Author: Cyrus Cooper ORCID iD
Author: Kay-Tee Khaw
Author: Ulf Ekelund
Author: Nicholas J. Wareham
Author: Ruth J.F. Loos

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