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BackgroundSingle nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.AimWe conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.Methods and findingsParticipants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷).ConclusionsWe found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Original publication

DOI

10.1371/journal.pone.0017436

Type

Journal article

Journal

PloS one

Publication Date

02/2011

Volume

6

Addresses

National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. huaidong.du@ctsu.ox.ac.uk

Keywords

Hypothalamus, Nerve Net, Humans, Genetic Predisposition to Disease, Body Weight, Weight Gain, Cohort Studies, Signal Transduction, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male, Young Adult