SynthesisPLoS genetics2009
Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?
Synthesis in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- The Genetic Basis of Childhood Obesity: A Systematic Review.Nutrients · 2023Pooled it
- Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.Human molecular genetics · 2015Pooled it
- Pooled it
- Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children.International journal of molecular sciences · 2023Article
- Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans.International journal of molecular sciences · 2022Article
- Associations of theJournal of personalized medicine · 2021Article
- Pharmacogenetic Correlates of Antipsychotic-Induced Weight Gain in the Chinese Population.Neuroscience bulletin · 2019Review
- Article
- Alzheimer's Disease Sequencing Project discovery and replication criteria for cases and controls: Data from a community-based prospective cohort study with autopsy follow-up.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Article
- Impact of home visit capacity on genetic association studies of late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Article
- Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North IndiaIranian biomedical journal · 2017Article
- Genetic association of left ventricular mass assessed by M-mode and two-dimensional echocardiography.Journal of hypertension · 2016Article
- Meta-analysis in clinical trials revisited.Contemporary clinical trials · 2015Article
- Gender-Specific Effect of -102G>A Polymorphism in Insulin Induced Gene 2 on Obesity in Chinese Children.International journal of endocrinology · 2015Article
- Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R.European journal of human genetics : EJHG · 2014Article
- Ovine insulin induced-gene-2: molecular characterization, polymorphisms and association with milk traits.Molecular biology reports · 2014Article
- Meta-analysis of sequencing studies with heterogeneous genetic associations.Genetic epidemiology · 2014Article
- Findings from the Quebec Family Study on the Etiology of Obesity: Genetics and Environmental Highlights.Current obesity reports · 2014Review
- FTO and INSIG2 Genotyping Combined with Metabolic and Anthropometric Phenotyping of Morbidly Obese Patients.Molecular syndromology · 2013Article
- Meta-analysis methods for genome-wide association studies and beyond.Nature reviews. Genetics · 2013Review
Corrections and comments
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Authors and funding
65 authors at 20 institutions in 14 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.