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Lyon, H.N.* ; Emilsson, V.* ; Hinney, A.* ; Heid, I.M. ; Lasky-Su, J.* ; Zhu, X.* ; Thorleifsson, G.* ; Gunnarsdottir, S.* ; Walters, G.B.* ; Thorsteinsdottir, U.* ; Kong, A.* ; Gulcher, J.* ; Nguyen, T.T.* ; Scherag, A.* ; Pfeufer, A. ; Meitinger, T. ; Brönner, G.* ; Rief, W.* ; Soto-Quiros, M.E.* ; Avila, L.* ; Klanderman, B.* ; Raby, B.A.* ; Silverman, E.K.* ; Weiss, S.T.* ; Laird, N.* ; Ding, X.* ; Groop, L.* ; Tuomi, T.* ; Isomaa, B.* ; Bengtsson, K.* ; Butler, J.L.* ; Cooper, R.S.* ; Fox, C.S.* ; O'Donnell, C.J.* ; Vollmert, C. ; Celedón, J.C.* ; Wichmann, H.-E. ; Hebebrand, J.* ; Stefansson, K.* ; Lange, C.* ; Hirschhorn, J.N.*

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

PLoS Genet. 3, 0627-0633:e61 (2007)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Human obesity; Gene risk; Polymorphism; Prevalence; Phenotypes; Variants; Proteins; Families; Disease
Sprache englisch
Veröffentlichungsjahr 2007
HGF-Berichtsjahr 0
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 3, Heft: 4, Seiten: 0627-0633, Artikelnummer: e61 Supplement: ,
Verlag Public Library of Science (PLoS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503900-001
G-500700-001
PubMed ID 17465681
DOI 10.1371/journal.pgen.0030061
WOS ID 000246041700017
Scopus ID 34247576412
Erfassungsdatum 2007-08-03
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