Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?: e1000694

• Published in: PLoS genetics 2009-10, Vol.5 (10)
• Main Authors: Heid, Iris M, Huth, Cornelia, Loos, Ruth JF, Kronenberg, Florian, Adamkova, Vera, Anand, Sonia S, Ardlie, Kristin, Biebermann, Heike, Bjerregaard, Peter, Boeing, Heiner, Bouchard, Claude, Ciullo, Marina, Cooper, Jackie A, Corella, Dolores, Dina, Christian, Engert, James C, Fisher, Eva, Francès, Francesc, Froguel, Philippe, Hebebrand, Johannes, Hegele, Robert A, Hinney, Anke, Hoehe, Margret R, Hu, Frank B, Hubacek, Jaroslav A, Humphries, Steve E, Hunt, Steven C, Illig, Thomas, Järvelin, Marjo-Riita, Kaakinen, Marika, Kollerits, Barbara, Krude, Heiko, Kumar, Jitender, Lange, Leslie A, Langer, Birgit, Li, Shengxu, Luchner, Andreas, Lyon, Helen N, Meyre, David, Mohlke, Karen L, Mooser, Vincent, Nebel, Almut, Nguyen, Thuy Trang, Paulweber, Bernhard, Perusse, Louis, Qi, Lu, Rankinen, Tuomo, Rosskopf, Dieter, Schreiber, Stefan, Sengupta, Shantanu, Sorice, Rossella, Suk, Anita, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Völzke, Henry, Vimaleswaran, Karani S, Wareham, Nicholas J, Waterworth, Dawn, Yusuf, Salim, Lindgren, Cecilia, McCarthy, Mark I, Lange, Christoph, Hirschhorn, Joel N, Laird, Nan, Wichmann, H-Erich
• Format: Article
• Language: English
• Subjects: Estimates; Genomes; Genotype & phenotype; Health sciences; Hypotheses; Medical research; Meta-analysis; Obesity; Studies
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000694

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