Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R

被引：0
作者：
Dörthe Malzahn
Martina Müller-Nurasyid
Iris M Heid
H-Erich Wichmann
Heike Bickeböller
机构：
[1] University Medical Center,Department of Genetic Epidemiology
[2] Georg-August-University,Department of Medicine I
[3] University Hospital Grosshadern,Department of Genetic Epidemiology
[4] Ludwig-Maximilians-University,undefined
[5] Institute of Medical Informatics,undefined
[6] Biometry and Epidemiology,undefined
[7] Chair of Epidemiology and Chair of Genetic Epidemiology,undefined
[8] Ludwig-Maximilians-University,undefined
[9] Institute of Genetic Epidemiology,undefined
[10] Helmholtz Zentrum München – German Research Center for Environmental Health,undefined
[11] University of Regensburg,undefined
[12] Institute of Epidemiology I,undefined
[13] Helmholtz Zentrum München – German Research Center for Environmental Health,undefined
[14] Institute of Medical Informatics,undefined
[15] Biometry and Epidemiology,undefined
[16] Chair of Epidemiology,undefined
[17] Ludwig-Maximilians-University,undefined
[18] Klinikum Großhadern,undefined
来源：
European Journal of Human Genetics | 2014年 / 22卷
关键词：
age dependence; body mass; cohort studies; genetic epistasis; longitudinal studies; obesity;
D O I：
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中图分类号：
学科分类号：
摘要：
Among the single-nucleotide polymorphisms (SNPs) previously reported to be associated with body mass index (BMI) and obesity, we focus on a common risk variant rs7566605 upstream of the insulin-induced gene 2 (INSIG2) gene and a rare protective variant rs2229616 on the melanocortin-4 receptor (MC4R) gene. INSIG2 is involved in adipogenesis and MC4R effects hormonal appetite control in response to the amount of adipose tissue. The influence of rs2229616 (MC4R) on BMI and obesity has been confirmed repeatedly and insight into the underlying mechanism provided. However, a main effect of rs7566605 (INSIG2) is under debate because of inconsistent replications of association. Interaction of rs7566605 with age may offer an explanation. SNP–age and SNP–SNP interaction models were tested on independent individuals from three population-based longitudinal cohorts, restricting the analysis to an observed age of 25–74 years. KORA S3/F3, KORA S4/F4 (Augsburg, Germany, 1994–2005, 1999–2008), and Framingham-Offspring data (Framingham, USA, 1971–2001) were analysed, with a total sample size of N=6926 in the joint analysis. The effect of interaction between rs7566605 and age on BMI and obesity status is significant and consistent across studies. This new evidence for rs7566605 (INSIG2) complements previous research. In addition, the interaction effect of rs7566605 with the MC4R variant rs2229616 on BMI was observed. This effect size was three times larger than that in a previously reported single-locus main effect of rs2229616. This leads to the conclusion that SNP–age or SNP–SNP interactions can mask genetic effects for complex diseases if left unaccounted for.
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页码：1217 / 1224
页数：7
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