FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.
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. Howe...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016390&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849725912305631232 |
|---|---|
| author | Kathryn G Ewens Michelle R Jones Wendy Ankener Douglas R Stewart Margrit Urbanek Andrea Dunaif Richard S Legro Angela Chua Ricardo Azziz Richard S Spielman Mark O Goodarzi Jerome F Strauss |
| author_facet | Kathryn G Ewens Michelle R Jones Wendy Ankener Douglas R Stewart Margrit Urbanek Andrea Dunaif Richard S Legro Angela Chua Ricardo Azziz Richard S Spielman Mark O Goodarzi Jerome F Strauss |
| author_sort | Kathryn G Ewens |
| collection | DOAJ |
| description | 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 (χ(2) = 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. |
| format | Article |
| id | doaj-art-5aa4e5c8e7a347be916a2b69a3763120 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-5aa4e5c8e7a347be916a2b69a37631202025-08-20T03:10:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1639010.1371/journal.pone.0016390FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.Kathryn G EwensMichelle R JonesWendy AnkenerDouglas R StewartMargrit UrbanekAndrea DunaifRichard S LegroAngela ChuaRicardo AzzizRichard S SpielmanMark O GoodarziJerome F StraussPolycystic 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 (χ(2) = 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016390&type=printable |
| spellingShingle | Kathryn G Ewens Michelle R Jones Wendy Ankener Douglas R Stewart Margrit Urbanek Andrea Dunaif Richard S Legro Angela Chua Ricardo Azziz Richard S Spielman Mark O Goodarzi Jerome F Strauss FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PLoS ONE |
| title | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| title_full | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| title_fullStr | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| title_full_unstemmed | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| title_short | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| title_sort | fto and mc4r gene variants are associated with obesity in polycystic ovary syndrome |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016390&type=printable |
| work_keys_str_mv | AT kathryngewens ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT michellerjones ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT wendyankener ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT douglasrstewart ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT margriturbanek ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT andreadunaif ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT richardslegro ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT angelachua ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT ricardoazziz ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT richardsspielman ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT markogoodarzi ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome AT jeromefstrauss ftoandmc4rgenevariantsareassociatedwithobesityinpolycysticovarysyndrome |