The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts

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The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts

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dc.contributor.author Emilsson, Valur
dc.contributor.author Hinney, Anke
dc.contributor.author Heid, Iris M
dc.contributor.author Zhu, Xiaofeng
dc.contributor.author Thorleifsson, Gudmar
dc.contributor.author Gunnarsdottir, Steinunn
dc.contributor.author Walters, G. Bragi
dc.contributor.author Thorsteinsdottir, Unnur
dc.contributor.author Kong, Augustine
dc.contributor.author Gulcher, Jeffrey
dc.contributor.author Nguyen, Thuy Trang
dc.contributor.author Scherag, André
dc.contributor.author Pfeufer, Arne
dc.contributor.author Meitinger, Thomas
dc.contributor.author Brönner, Günter
dc.contributor.author Rief, Winfried
dc.contributor.author Soto-Quiros, Manuel E
dc.contributor.author Avila, Lydiana
dc.contributor.author Groop, Leif
dc.contributor.author Tuomi, Tiinamaija
dc.contributor.author Isomaa, Bo
dc.contributor.author Bengtsson, Kristina
dc.contributor.author Butler, Johannah L
dc.contributor.author Vollmert, Caren
dc.contributor.author Celedón, Juan C
dc.contributor.author Wichmann, H. Erich
dc.contributor.author Hebebrand, Johannes
dc.contributor.author Stefansson, Kari
dc.contributor.author Abecasis, Gonçalo
dc.contributor.author Lyon, Helen N
dc.contributor.author Su, Jessica Ann Lasky
dc.contributor.author Klanderman, Barbara Jordan
dc.contributor.author Raby, Benjamin Alexander
dc.contributor.author Silverman, Edwin Kepner
dc.contributor.author Weiss, Scott Tillman
dc.contributor.author Laird, Nan M.
dc.contributor.author Ding, Xiao
dc.contributor.author Cooper, Richard S
dc.contributor.author Fox, Caroline
dc.contributor.author O'Donnell, Christopher Joseph
dc.contributor.author Lange, Christoph
dc.contributor.author Hirschhorn, Joel Naom
dc.date.accessioned 2012-01-03T22:42:16Z
dc.date.issued 2007
dc.identifier.citation Lyon, Helen N., Valur Emilsson, Anke Hinney, Iris M. Heid, Jessica Lasky-Su, Xiaofeng Zhu, Gudmar Thorleifsson, et al. 2007. The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts. PLoS Genetics 3(4): e61. en_US
dc.identifier.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:6177593
dc.description.abstract A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.0030061 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857727/pdf/ en_US
dash.license LAA
dc.subject diabetes and endocrinology en_US
dc.subject genetics and genomics en_US
dc.subject public health and epidemiology en_US
dc.subject homo (human) en_US
dc.title The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Lyon, Helen N
dc.date.available 2012-01-03T22:42:16Z
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Molecular+Integrative Physiological Sci Prog en_US
dash.affiliation.other SPH^Biostatistics en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Biostatistics en_US
dash.affiliation.other HMS^Genetics en_US

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