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Kettunen, J.* ; Silander, K.* ; Saarela, O.* ; Amin, N.* ; Müller, M. ; Timpson, N.* ; Surakka, I.* ; Ripatti, S.* ; Laitinen, J.* ; Hartikainen, A.L.* ; Pouta, A.* ; Lahermo, P.* ; Anttila, V.* ; Männistö, S.* ; Jula, A.* ; Virtamo, J.* ; Salomaa, V.* ; Lehtimäki, T.* ; Raitakari, O.* ; Gieger, C. ; Wichmann, H.-E. ; van Duijn, C.M.* ; Smith, G.D.* ; McCarthy, M.I.* ; Jarvelin, M.R.* ; Perola, M.* ; Peltonen, L.*

European lactase persistence genotype shows evidence of association with increase in body mass index.

Hum. Mol. Genet. 19, 1129-1136 (2010)
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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 beta-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 x 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords GENOME-WIDE ASSOCIATION; ADULT-TYPE HYPOLACTASIA; DEFINED LACTOSE-MALABSORPTION; BRITISH WOMENS HEART; GEOGRAPHICAL VARIATION; CARDIOVASCULAR RISK; MILK CONSUMPTION; CALCIUM INTAKE; YOUNG FINNS; OBESITY
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 19, Issue: 6, Pages: 1129-1136 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)