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

Huaidong Du; Lars Henrik Ängquist; Karani S Vimaleswaran; Rikke D Hansen; Daphne L van der; 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

doi:10.1371/journal.pone.0017436

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

Huaidong Du, Lars Henrik Ängquist, Karani S Vimaleswaran, Rikke D Hansen, Daphne L van der, 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

21 Citations (Scopus)

Abstract

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 = 2×10^-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 language	English
Journal	P L o S One
Volume	6
Issue number	2
Pages (from-to)	e17436
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0017436 https://doi.org/10.1371/journal.pone.0017436
Publication status	Published - 2011

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Du, H., Ängquist, L. H., Vimaleswaran, K. S., Hansen, R. D., van der, D. L., Holst, C., Tjønneland, A., Overvad, K., Jakobsen, M. U., Boeing, H., Meidtner, K., Palli, D., Masala, G., Bouatia-Naji, N., Saris, W. H. M., Feskens, E. J. M., Wareham, N. J., Sørensen, T. I. A., & Loos, R. J. F. (2011). Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study. P L o S One, 6(2), e17436. https://doi.org/10.1371/journal.pone.0017436, https://doi.org/10.1371/journal.pone.0017436

Du, H, Ängquist, LH, Vimaleswaran, KS, Hansen, RD, van der, DL, Holst, C, Tjønneland, A, Overvad, K, Jakobsen, MU, Boeing, H, Meidtner, K, Palli, D, Masala, G, Bouatia-Naji, N, Saris, WHM, Feskens, EJM, Wareham, NJ, Sørensen, TIA & Loos, RJF 2011, 'Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study', P L o S One, vol. 6, no. 2, pp. e17436. https://doi.org/10.1371/journal.pone.0017436, https://doi.org/10.1371/journal.pone.0017436

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title = "Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study",

abstract = "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 = 2×10-7). 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.",

author = "Huaidong Du and {\"A}ngquist, {Lars Henrik} and Vimaleswaran, {Karani S} and Hansen, {Rikke D} and {van der}, {Daphne L} and Claus Holst and Anne Tj{\o}nneland and Kim Overvad and Jakobsen, {Marianne Uhre} and Heiner Boeing and Karina Meidtner and Domenico Palli and Giovanna Masala and Nabila Bouatia-Naji and Saris, {Wim H M} and Feskens, {Edith J M} and Wareham, {Nicolas J} and S{\o}rensen, {Thorkild I A} and Loos, {Ruth J F}",

year = "2011",

doi = "10.1371/journal.pone.0017436",

language = "English",

volume = "6",

pages = "e17436",

journal = "PLoS Computational Biology",

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TY - JOUR

T1 - Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

AU - Du, Huaidong

AU - Ängquist, Lars Henrik

AU - Vimaleswaran, Karani S

AU - Hansen, Rikke D

AU - van der, Daphne L

AU - Holst, Claus

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Jakobsen, Marianne Uhre

AU - Boeing, Heiner

AU - Meidtner, Karina

AU - Palli, Domenico

AU - Masala, Giovanna

AU - Bouatia-Naji, Nabila

AU - Saris, Wim H M

AU - Feskens, Edith J M

AU - Wareham, Nicolas J

AU - Sørensen, Thorkild I A

AU - Loos, Ruth J F

PY - 2011

Y1 - 2011

N2 - 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 = 2×10-7). 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.

AB - 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 = 2×10-7). 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.

U2 - 10.1371/journal.pone.0017436

DO - 10.1371/journal.pone.0017436

M3 - Journal article

SN - 1932-6203

VL - 6

SP - e17436

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 2

ER -

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

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