Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?

Details

Serval ID
serval:BIB_E70F6FB39F40
Type
Article: article from journal or magazin.
Collection
Publications
Title
Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?
Journal
Plos Genetics
Author(s)
Heid I.M., Huth C., Loos R.J., Kronenberg F., Adamkova V., Anand S.S., Ardlie K., Biebermann H., Bjerregaard P., Boeing H., Bouchard C., Ciullo M., Cooper J.A., Corella D., Dina C., Engert J.C., Fisher E., Francès F., Froguel P., Hebebrand J., Hegele R.A., Hinney A., Hoehe M.R., Hu F.B., Hubacek J.A., Humphries S.E., Hunt S.C., Illig T., Järvelin M.R., Kaakinen M., Kollerits B., Krude H., Kumar J., Lange L.A., Langer B., Li S., Luchner A., Lyon H.N., Meyre D., Mohlke K.L., Mooser V., Nebel A., Nguyen T.T., Paulweber B., Perusse L., Qi L., Rankinen T., Rosskopf D., Schreiber S., Sengupta S., Sorice R., Suk A., Thorleifsson G., Thorsteinsdottir U., Völzke H., Vimaleswaran K.S., Wareham N.J., Waterworth D., Yusuf S., Lindgren C., McCarthy M.I., Lange C., Hirschhorn J.N., Laird N., Wichmann H.E.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
5
Number
10
Pages
e1000694
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Abstract
The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.
Keywords
Adolescent, Adult, Female, Genetics, Population, Genome-Wide Association Study/standards, Humans, Intracellular Signaling Peptides and Proteins/genetics, Male, Membrane Proteins/genetics, Middle Aged, Obesity/epidemiology, Obesity/genetics, Polymorphism, Genetic, Research Design/standards, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
21/01/2013 10:56
Last modification date
20/08/2019 16:10
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