Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change - the DiOGenes study

Huaidong Du, Karani S. Vimaleswaran, Lars Angquist, Rikke D. Hansen, Daphne L. van der A, Claus Holst, Anne Tjønneland, Kim Overvad, Marianne Uhre Jakobsen, Heiner Boeing, Karina Meidtner, Domenico Palli, Giovanna Masala, Nabila Bouatia-Naji, Wim H. M. Saris, Edith J. M. Feskens, Nicolas J. Wareham, Thorkild I. A. Sørensen, Ruth J. F. Loos

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BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We 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 FINDINGS: Participants, 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). CONCLUSIONS: We 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 languageEnglish
Article numbere17436
JournalP L o S One
Issue number2
Number of pages8
Publication statusPublished - 2011
Externally publishedYes


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