The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts

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title = "The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts",
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.",
author = "Lyon, {Helen N.} and Valur Emilsson and Anke Hinney and Heid, {Iris M.} and Jessica Lasky-Su and Xiaofeng Zhu and Gudmar Thorleifsson and Steinunn Gunnarsdottir and Walters, {G. Bragi} and Unnur Thorsteinsdottir and Augustine Kong and Jeffrey Gulcher and Nguyen, {Thuy Trang} and Andre Scherag and Arne Pfeufer and Thomas Meitinger and Guenter Broenner and Winfried Rief and Soto-Quiros, {Manuel E.} and Lydiana Avila and Barbara Klanderman and Raby, {Benjamin A.} and Silverman, {Edwin K.} and Weiss, {Scott T.} and Nan Laird and Xiao Ding and Leif Groop and Tiinamaija Tuomi and Bo Isomaa and Kristina Bengtsson and Butler, {Johannah L.} and Cooper, {Richard S.} and Fox, {Caroline S.} and O'Donnell, {Christopher J.} and Caren Vollmert and Celedon, {Juan C.} and Wichmann, {H. Erich} and Johannes Hebebrand and Kari Stefansson and Christoph Lange and Hirschhorn, {Joel N.}",
year = "2007",
doi = "10.1371/journal.pgen.0030061",
language = "English",
volume = "3",
journal = "PLoS Genetics",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "4",