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Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: Does heterogeneity of estimates relate to study design?
PLoS Genet. 5:e1000694 (2009)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
8.883
1.120
50
57
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
COMMON GENETIC VARIANT; METABOLIC SYNDROME; BODY-MASS; POLYMORPHISM; LIVER; POPULATION; EXPRESSION; UPSTREAM; INSULIN; PROTEIN
Sprache
englisch
Veröffentlichungsjahr
2009
HGF-Berichtsjahr
0
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Zeitschrift
PLoS Genetics
Quellenangaben
Band: 5,
Heft: 10,
Artikelnummer: e1000694
Verlag
Public Library of Science (PLoS)
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-503900-001
PubMed ID
19851442
WOS ID
000272032100032
Scopus ID
73449085512
Erfassungsdatum
2009-12-11