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. / Lyon, Helen N.; Emilsson, Valur; Hinney, Anke; Heid, Iris M.; Lasky-Su, Jessica; Zhu, Xiaofeng; Thorleifsson, Gudmar; Gunnarsdottir, Steinunn; Walters, G. Bragi; Thorsteinsdottir, Unnur; Kong, Augustine; Gulcher, Jeffrey; Nguyen, Thuy Trang; Scherag, Andre; Pfeufer, Arne; Meitinger, Thomas; Broenner, Guenter; Rief, Winfried; Soto-Quiros, Manuel E.; Avila, Lydiana; Klanderman, Barbara; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.; Laird, Nan; Ding, Xiao; Groop, Leif; Tuomi, Tiinamaija; Isomaa, Bo; Bengtsson, Kristina; Butler, Johannah L.; Cooper, Richard S.; Fox, Caroline S.; O'Donnell, Christopher J.; Vollmert, Caren; Celedon, Juan C.; Wichmann, H. Erich; Hebebrand, Johannes; Stefansson, Kari; Lange, Christoph; Hirschhorn, Joel N.

I: PLoS Genetics, Vol. 3, Nr. 4, 2007.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Lyon, HN, Emilsson, V, Hinney, A, Heid, IM, Lasky-Su, J, Zhu, X, Thorleifsson, G, Gunnarsdottir, S, Walters, GB, Thorsteinsdottir, U, Kong, A, Gulcher, J, Nguyen, TT, Scherag, A, Pfeufer, A, Meitinger, T, Broenner, G, Rief, W, Soto-Quiros, ME, Avila, L, Klanderman, B, Raby, BA, Silverman, EK, Weiss, ST, Laird, N, Ding, X, Groop, L, Tuomi, T, Isomaa, B, Bengtsson, K, Butler, JL, Cooper, RS, Fox, CS, O'Donnell, CJ, Vollmert, C, Celedon, JC, Wichmann, HE, Hebebrand, J, Stefansson, K, Lange, C & Hirschhorn, JN 2007, 'The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts', PLoS Genetics, vol. 3, nr. 4. https://doi.org/10.1371/journal.pgen.0030061

APA

Lyon, H. N., Emilsson, V., Hinney, A., Heid, I. M., Lasky-Su, J., Zhu, X., ... Hirschhorn, J. N. (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). https://doi.org/10.1371/journal.pgen.0030061

CBE

Lyon HN, Emilsson V, Hinney A, Heid IM, Lasky-Su J, Zhu X, Thorleifsson G, Gunnarsdottir S, Walters GB, Thorsteinsdottir U, Kong A, Gulcher J, Nguyen TT, Scherag A, Pfeufer A, Meitinger T, Broenner G, Rief W, Soto-Quiros ME, Avila L, Klanderman B, Raby BA, Silverman EK, Weiss ST, Laird N, Ding X, Groop L, Tuomi T, Isomaa B, Bengtsson K, Butler JL, Cooper RS, Fox CS, O'Donnell CJ, Vollmert C, Celedon JC, Wichmann HE, Hebebrand J, Stefansson K, Lange C, Hirschhorn JN. 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). https://doi.org/10.1371/journal.pgen.0030061

MLA

Vancouver

Author

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

RIS

TY - JOUR

T1 - The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts

AU - Lyon, Helen N.

AU - Emilsson, Valur

AU - Hinney, Anke

AU - Heid, Iris M.

AU - Lasky-Su, Jessica

AU - Zhu, Xiaofeng

AU - Thorleifsson, Gudmar

AU - Gunnarsdottir, Steinunn

AU - Walters, G. Bragi

AU - Thorsteinsdottir, Unnur

AU - Kong, Augustine

AU - Gulcher, Jeffrey

AU - Nguyen, Thuy Trang

AU - Scherag, Andre

AU - Pfeufer, Arne

AU - Meitinger, Thomas

AU - Broenner, Guenter

AU - Rief, Winfried

AU - Soto-Quiros, Manuel E.

AU - Avila, Lydiana

AU - Klanderman, Barbara

AU - Raby, Benjamin A.

AU - Silverman, Edwin K.

AU - Weiss, Scott T.

AU - Laird, Nan

AU - Ding, Xiao

AU - Groop, Leif

AU - Tuomi, Tiinamaija

AU - Isomaa, Bo

AU - Bengtsson, Kristina

AU - Butler, Johannah L.

AU - Cooper, Richard S.

AU - Fox, Caroline S.

AU - O'Donnell, Christopher J.

AU - Vollmert, Caren

AU - Celedon, Juan C.

AU - Wichmann, H. Erich

AU - Hebebrand, Johannes

AU - Stefansson, Kari

AU - Lange, Christoph

AU - Hirschhorn, Joel N.

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.0030061

DO - 10.1371/journal.pgen.0030061

M3 - Article

VL - 3

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7404

IS - 4

ER -