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dc.contributor.authorHeid, Iris M.
dc.contributor.authorHuth, Cornelia
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorKronenberg, Florian
dc.contributor.authorAdamkova, Vera
dc.contributor.authorAnand, Sonia S.
dc.contributor.authorArdlie, Kristin
dc.contributor.authorBiebermann, Heike
dc.contributor.authorBjerregaard, Peter
dc.contributor.authorBoeing, Heiner
dc.contributor.authorBouchard, Claude
dc.contributor.authorCiullo, Marina
dc.contributor.authorCooper, Jackie A.
dc.contributor.authorCorella, Dolores
dc.contributor.authorDina, Christian
dc.contributor.authorEngert, James C.
dc.contributor.authorFisher, Eva
dc.contributor.authorFrancès, Francesc
dc.contributor.authorFroguel, Philippe
dc.contributor.authorHebebrand, Johannes
dc.contributor.authorHegele, Robert A.
dc.contributor.authorHinney, Anke
dc.contributor.authorHoehe, Margret R.
dc.contributor.authorHubacek, Jaroslav A.
dc.contributor.authorHumphries, Steve E.
dc.contributor.authorHunt, Steven C.
dc.contributor.authorIllig, Thomas
dc.contributor.authorJärvelin, Marjo-Riita
dc.contributor.authorKaakinen, Marika
dc.contributor.authorKollerits, Barbara
dc.contributor.authorKrude, Heiko
dc.contributor.authorKumar, Jitender
dc.contributor.authorLange, Leslie A.
dc.contributor.authorLanger, Birgit
dc.contributor.authorLi, Shengxu
dc.contributor.authorLuchner, Andreas
dc.contributor.authorMeyre, David
dc.contributor.authorMohlke, Karen L.
dc.contributor.authorMooser, Vincent
dc.contributor.authorNebel, Almut
dc.contributor.authorNguyen, Thuy Trang
dc.contributor.authorPaulweber, Bernhard
dc.contributor.authorPerusse, Louis
dc.contributor.authorRankinen, Tuomo
dc.contributor.authorRosskopf, Dieter
dc.contributor.authorSchreiber, Stefan
dc.contributor.authorSengupta, Shantanu
dc.contributor.authorSorice, Rossella
dc.contributor.authorSuk, Anita
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorVölzke, Henry
dc.contributor.authorVimaleswaran, Karani S.
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorWaterworth, Dawn
dc.contributor.authorYusuf, Salim
dc.contributor.authorLindgren, Cecilia
dc.contributor.authorMcCarthy, Mark I.
dc.contributor.authorWichmann, H.-Erich
dc.contributor.authorAllison, David B.
dc.contributor.authorHu, Frank B.
dc.contributor.authorQi, Lu
dc.contributor.authorLyon, Helen N
dc.contributor.authorLange, Christoph
dc.contributor.authorHirschhorn, Joel Naom
dc.contributor.authorLaird, Nan M.
dc.date.accessioned2012-01-05T04:20:39Z
dc.date.issued2009
dc.identifier.citationHeid, Iris M., Cornelia Huth, Ruth J. F. Loos, Florian Kronenberg, Vera Adamkova, Sonia S. Anand, Kristin Ardlie, et al. 2009. Meta-Analysis of the INSIG2 association with obesity including 74,345 individuals: Does heterogeneity of estimates relate to study design? PLoS Genetics 5(10): e1000694.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:6518814
dc.description.abstractThe 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 less than;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 importance of study design might be under-recognized in gene discovery and association replication so far.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1000694en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757909/pdf/en_US
dash.licenseLAA
dc.subjectpublic healthen_US
dc.subjectepidemiologyen_US
dc.titleMeta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorHu, Frank B.
dc.date.available2012-01-05T04:20:39Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Nutritionen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Nutritionen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Biostatisticsen_US
dash.affiliation.otherHMS^Geneticsen_US
dash.affiliation.otherSPH^Biostatisticsen_US
dc.identifier.doi10.1371/journal.pgen.1000694*
dash.authorsorderedfalse
dash.contributor.affiliatedLyon, Helen N.
dash.contributor.affiliatedLaird, Nan
dash.contributor.affiliatedLange, Christoph
dash.contributor.affiliatedHirschhorn, Joel
dash.contributor.affiliatedQi, Lu
dash.contributor.affiliatedHu, Frank


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