دورية أكاديمية
Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?
| العنوان: | Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design? |
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| المؤلفون: | Heid, IM, Huth, C, Loos, RJF, Kronenberg, F, Adamkova, V, Anand, SS, Ardlie, K, Biebermann, H, Bjerregaard, P, Boeing, H, Bouchard, C, Ciullo, M, Cooper, JA, Corella, D, Dina, C, Engert, JC, Fisher, E, Frances, F, Froguel, P, Hebebrand, J, Hegele, RA, Hinney, A, Hoehe, MR, Hu, FB, Hubacek, JA, Humphries, SE, Hunt, SC, Illig, T, Jarvelin, M-R, Kaakinen, M, Kollerits, B, Krude, H, Kumar, J, Lange, LA, Langer, B, Li, S, Luchner, A, Lyon, HN, Meyre, D, Mohlke, KL, Mooser, V, Nebel, A, Nguyen, TT, Paulweber, B, Perusse, L, Qi, L, Rankinen, T, Rosskopf, D, Schreiber, S, Sengupta, S, Sorice, R, Suk, A, Thorleifsson, G, Thorsteinsdottir, U, Voelzke, H, Vimaleswaran, KS, Wareham, NJ, Waterworth, D, Yusuf, S, Lindgren, C, McCarthy, MI, Lange, C, Hirschhorn, JN, Laird, N, Wichmann, H-E |
| المساهمون: | Medical Research Council (MRC) |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2009 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, COMMON GENETIC VARIANT, METABOLIC SYNDROME, BODY-MASS, POLYMORPHISM, LIVER, POPULATION, EXPRESSION, UPSTREAM, INSULIN, PROTEIN, Adolescent, Adult, Female, Genetics, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Middle Aged, Obesity, Genetic, Research Design, Young Adult, Developmental Biology, 0604 Genetics |
| الوصف: | 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<25 kg/m2) 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1553-7390 |
| العلاقة: | PLOS Genetics; http://hdl.handle.net/10044/1/48222Test; https://dx.doi.org/10.1371/journal.pgen.1000694Test; G0600331 |
| DOI: | 10.1371/journal.pgen.1000694 |
| الإتاحة: | https://doi.org/10.1371/journal.pgen.1000694Test http://hdl.handle.net/10044/1/48222Test |
| حقوق: | © 2009 Heid et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0Test/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| رقم الانضمام: | edsbas.F6181F99 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15537390 |
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| DOI: | 10.1371/journal.pgen.1000694 |