FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome

Kathryn G. Ewens, Michelle R. Jones, Wendy Ankener, Douglas R. Stewart, Margrit Urbanek, Andrea Dunaif, Richard Legro, Angela Chua, Ricardo Azziz, Richard S. Spielman, Mark O. Goodarzi, Jerome F. Strauss

Research output: Contribution to journalArticle

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Abstract

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (x2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative- TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.

Original languageEnglish (US)
Article numbere16390
JournalPloS one
Volume6
Issue number1
DOIs
StatePublished - Feb 3 2011

Fingerprint

polycystic ovary syndrome
Polycystic Ovary Syndrome
obesity
Obesity
Genes
Single Nucleotide Polymorphism
genes
Medical problems
Case-Control Studies
case-control studies
Phenotype
phenotype
menstrual cycle
Genome-Wide Association Study
Genetic Predisposition to Disease
Menstrual Cycle
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Infertility
linkage (genetics)

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ewens, K. G., Jones, M. R., Ankener, W., Stewart, D. R., Urbanek, M., Dunaif, A., ... Strauss, J. F. (2011). FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PloS one, 6(1), [e16390]. https://doi.org/10.1371/journal.pone.0016390
Ewens, Kathryn G. ; Jones, Michelle R. ; Ankener, Wendy ; Stewart, Douglas R. ; Urbanek, Margrit ; Dunaif, Andrea ; Legro, Richard ; Chua, Angela ; Azziz, Ricardo ; Spielman, Richard S. ; Goodarzi, Mark O. ; Strauss, Jerome F. / FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. In: PloS one. 2011 ; Vol. 6, No. 1.
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Ewens, KG, Jones, MR, Ankener, W, Stewart, DR, Urbanek, M, Dunaif, A, Legro, R, Chua, A, Azziz, R, Spielman, RS, Goodarzi, MO & Strauss, JF 2011, 'FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome', PloS one, vol. 6, no. 1, e16390. https://doi.org/10.1371/journal.pone.0016390

FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. / Ewens, Kathryn G.; Jones, Michelle R.; Ankener, Wendy; Stewart, Douglas R.; Urbanek, Margrit; Dunaif, Andrea; Legro, Richard; Chua, Angela; Azziz, Ricardo; Spielman, Richard S.; Goodarzi, Mark O.; Strauss, Jerome F.

In: PloS one, Vol. 6, No. 1, e16390, 03.02.2011.

Research output: Contribution to journalArticle

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T1 - FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome

AU - Ewens, Kathryn G.

AU - Jones, Michelle R.

AU - Ankener, Wendy

AU - Stewart, Douglas R.

AU - Urbanek, Margrit

AU - Dunaif, Andrea

AU - Legro, Richard

AU - Chua, Angela

AU - Azziz, Ricardo

AU - Spielman, Richard S.

AU - Goodarzi, Mark O.

AU - Strauss, Jerome F.

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Y1 - 2011/2/3

N2 - Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (x2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative- TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.

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Ewens KG, Jones MR, Ankener W, Stewart DR, Urbanek M, Dunaif A et al. FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PloS one. 2011 Feb 3;6(1). e16390. https://doi.org/10.1371/journal.pone.0016390