Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

Iris M Heid, Cornelia Huth, Ruth J F Loos, Florian Kronenberg, Vera Adamkova, Sonia S Anand, Kristin Ardlie, Heike Biebermann, Peter Bjerregaard, Heiner Boeing, Claude Bouchard, Marina Ciullo, Jackie A Cooper, Dolores Corella, Christian Dina, James C Engert, Eva Fisher, Francesc Francès, Philippe Froguel, Johannes Hebebrand, Robert A Hegele, Anke Hinney, Margret R Hoehe, Frank B Hu, Jaroslav A Hubacek, Steve E Humphries, Steven C Hunt, Thomas Illig, Marjo-Riita Järvelin, Marika Kaakinen, Barbara Kollerits, Heiko Krude, Jitender Kumar, Leslie A Lange, Birgit Langer, Shengxu Li, Andreas Luchner, Helen N Lyon, David Meyre, Karen L Mohlke, Vincent Mooser, Almut Nebel, Thuy Trang Nguyen, Bernhard Paulweber, Louis Perusse, Lu Qi, Tuomo Rankinen, Dieter Rosskopf, Stefan Schreiber, Shantanu Sengupta, Rossella Sorice, Anita Suk, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Henry Völzke, Karani S Vimaleswaran, Nicholas J Wareham, Dawn Waterworth, Salim Yusuf, Cecilia Lindgren, Mark I McCarthy, Christoph Lange, Joel N Hirschhorn, Nan Laird and H-Erich Wichmann

PLOS Genetics, 2009, vol. 5, issue 10, 1-10

Abstract: The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) 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 I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 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≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI

Date: 2009
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1000694

DOI: 10.1371/journal.pgen.1000694

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