European lactase persistence genotype shows evidence of association with increase in body mass index
Author(s)
Type
Journal Article
Abstract
The global prevalence of obesity has increased significantly in recent decades, mainly due to excess calorie intake and increasingly sedentary lifestyle. Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis -regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We genetically defined lactase persistence (LP) in 31 720 individuals from eight European population-based studies and one family study by genotyping or imputing the European LP variant (rs4988235). We performed a meta-analysis by pooling the β-coefficient estimates of the relationship between rs4988235 and BMI from the nine studies and found that the carriers of the allele responsible for LP among Europeans showed higher BMI ( P = 7.9 × 10 −5 ). Since this locus has been shown to be prone to population stratification, we paid special attention to reveal any population substructure which might be responsible for the association signal. The best evidence of exclusion of stratification came from the Dutch family sample which is robust for stratification. In this study, we highlight issues in model selection in the genome-wide association studies and problems in imputation of these special genomic regions.
Date Issued
2010-03-15
Date Acceptance
2009-12-14
Citation
Human Molecular Genetics, 2010, 19 (6), pp.1129-1136
ISSN
0964-6906
Publisher
Oxford University Press (OUP)
Start Page
1129
End Page
1136
Journal / Book Title
Human Molecular Genetics
Volume
19
Issue
6
Copyright Statement
© The Author 2009. Published by Oxford University Press
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000275262500016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
DEFINED LACTOSE-MALABSORPTION
GENOME-WIDE ASSOCIATION
ADULT-TYPE HYPOLACTASIA
BRITISH WOMENS HEART
GEOGRAPHICAL VARIATION
CARDIOVASCULAR RISK
MILK CONSUMPTION
CALCIUM INTAKE
OBESITY
VARIANT
Publication Status
Published
Date Publish Online
2009-12-16