Genome-wide association study identifies GYS2 as a novel genetic factor for polycystic ovary syndrome through obesity-related condition

Journal of Human Genetics

Volumn 57, Issue 10, 2012, Pages 660-664

  Hwang, Joo Yeon ^a   Lee, Eun Ju ^a   Jin Go, Min ^a   Sung, Yeon Ah ^b   Lee, Hye Jin ^b   Heon Kwak, Soo ^c   Jang, Hak C ^c   Soo Park, Kyung ^c,d   Lee, Hye Ja ^a   Byul Jang, Han ^a   Song, Jihyun ^a   Park, Kyung Hee ^e   Kim, Hyung Lae ^b   Cho, Myeong Chan ^a   Lee, Jong Young ^a  

^a Korea National Institute of Health   (South Korea)

^b Ewha Womans University School of Medicine   (South Korea)

^c Seoul National University College of Medicine   (South Korea)

^d Seoul National University   (South Korea)

^e Hallym University   (South Korea)

Author keywords

GWAS; obesity; PCOS; pleiotropic effect

Indexed keywords

GYS2 PROTEIN; PROTEIN; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BODY MASS; CHILDHOOD OBESITY; CONTROLLED STUDY; FEMALE; GENE IDENTIFICATION; GENE LOCUS; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HEREDITY; HUMAN; KOREA; MAJOR CLINICAL STUDY; METABOLIC REGULATION; OBESITY; OVARY POLYCYSTIC DISEASE; PATHOGENESIS; PLEIOTROPY; PREGNANCY DIABETES MELLITUS;

ADULT; AMENORRHEA; ASIAN CONTINENTAL ANCESTRY GROUP; BODY MASS INDEX; CASE-CONTROL STUDIES; CHILD; DIABETES, GESTATIONAL; FEMALE; GENE FREQUENCY; GENETIC PLEIOTROPY; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; OBESITY; OLIGOMENORRHEA; POLYCYSTIC OVARY SYNDROME; POLYMORPHISM, SINGLE NUCLEOTIDE; PREGNANCY; RISK FACTORS; YOUNG ADULT;

EID: 84867921300     PISSN: 14345161     EISSN: 1435232X     Source Type: Journal    
DOI: 10.1038/jhg.2012.92     Document Type: Article

References (42)

1. Glintborg, D. & Andersen, M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol. Endocrinol. 26, 281-296 (2010
2. Diamanti-Kandarakis, E., Xyrafis, X., Boutzios, G. & Christakou, C. Pancreatic betacells dysfunction in polycystic ovary syndrome. Panminerva Med. 50, 315-325 (2008
3. Biyasheva, A., Legro, R. S., Dunaif, A. & Urbanek, M. Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2. J. Clin. Endocrinol. Metab. 94, 2617-2625 (2009
4. Corbett, S. J., McMichael, A. J. & Prentice, A. M. Type 2 diabetes, cardiovascular disease, and the evolutionary paradox of the polycystic ovary syndrome: A fertility first hypothesis. Am. J. Hum. Biol. 21, 587-598 (2009
5. Dasgupta, S., Sirisha, P. V., Neelaveni, K., Anuradha, K. & Reddy, B. M. Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women. PLoS One 7, e32192 (2012
6. Goodarzi, M. O., Jones, M. R., Chen, Y. D. & Azziz, R. First evidence of genetic association between AKT2 and polycystic ovary syndrome. Diabetes Care 31, 2284-2287 (2008
7. Goodarzi, M. O., Jones, M. R., Li, X., Chua, A. K., Garcia, O. A., Chen, Y. D. et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J. Med. Genet. 49, 90-95 (2012
8. Lerchbaum, E., Trummer, O., Giuliani, A., Gruber, H. J., Pieber, T. R. & Obermayer- Pietsch, B. Susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21, and 9q33.3 in a cohort of Caucasian women. Horm. Metab. Res. 43, 743-747 (2011
9. Zhao, H., Xu, X., Xing, X., Wang, J., He, L., Shi, Y. et al. Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Hum. Reprod. 27, 294-298 (2012
10. Chen, Z. J., Zhao, H., He, L., Shi, Y., Qin, Y., Li, Z. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat. Genet. 43, 55-59 (2011
11. Jones, M. R., Chua, A. K., Mengesha, E. A., Taylor, K. D., Chen, Y. D., Li, X. et al. Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS). Steroids 77, 317-322 (2012
12. Hanzu, F. A., Radian, S., Attaoua, R., Ait-El-Mkadem, S., Fica, S., Gheorghiu, M. et al. Association of insulin receptor genetic variants with polycystic ovary syndrome in a population of women from Central Europe. Fertil. Steril. 94, 2389-2392 (2010
13. Christopoulos, P., Mastorakos, G., Gazouli, M., Deligeoroglou, E., Katsikis, I., Diamanti- Kandarakis, E. et al. Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact? Gynecol. Endocrinol. 26, 698-703 (2010
14. Unluturk, U., Harmanci, A., Kocaefe, C. & Yildiz, B. O. The genetic basis of the polycystic ovary syndrome: A literature review including discussion of PPAR-gamma. PPAR Res. 2007, 49109 (2007
15. Attaoua, R., Ait El Mkadem, S., Radian, S., Fica, S., Hanzu, F., Albu, A. et al. FTO gene associates to metabolic syndrome in women with polycystic ovary syndrome. Biochem. Biophys. Res. Commun. 373, 230-234 (2008
16. Barber, T. M. & Franks, S. The link between polycystic ovary syndrome and both Type 1 and Type 2 diabetes mellitus: What do we know today? Womens Health 8, 147-154 (2012
17. Legro, R. S., Kunselman, A. R., Dodson, W. C. & Dunaif, A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women. J. Clin. Endocrinol. Metab. 84, 165-169 (1999
18. Motta, A. B. The role of obesity in the development of polycystic ovary syndrome. Curr. Pharm. Des. 18, 2482-2491 (2012
19. Escobar-Morreale, H. F., Samino, S., Insenser, M., Vinaixa, M., Luque-Ramirez, M., Lasuncion, M. A. et al. Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: Plasma metabolomic approach using GC-MS. Clin. Chem. 58, 999-1009 (2012
20. Kim, J. J., Choi, Y.M., Cho, Y. M., Hong, M. A., Chae, S. J., Hwang, K. R. et al. Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes. Clin. Endocrinol. 77, 439-445 (2012
21. Saxena, R. & Welt, C. K. Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes. Acta. Diabetol. (e-pub ahead of print 3 March 2012
22. Ewens, K. G., Jones, M. R., Ankener, W., Stewart, D. R., Urbanek, M., Dunaif, A. et al. Type 2 diabetes susceptibility single-nucleotide polymorphisms are not associated with polycystic ovary syndrome. Fertil. Steril. 95, 2538-2541 e1-6 (2011
23. Zhang, X., Fu, L., Zhang, Q., Yan, L., Ma, Y., Tu, B. et al. Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women. Reprod. Biol. Endocrinol. 9, 46 (2011
24. Ewens, K. G., Jones, M. R., Ankener, W., Stewart, D. R., Urbanek, M., Dunaif, A. et al. FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PLoS One 6, e16390 (2011
25. Barber, T. M., Bennett, A. J., Groves, C. J., Sovio, U., Ruokonen, A., Martikainen, H. et al. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 51, 1153-1158 (2008
26. Wehr, E., Schweighofer, N., Moller, R., Giuliani, A., Pieber, T. R. & Obermayer- Pietsch, B. Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome. Metabolism 59, 575-580 (2011
27. Tan, S., Scherag, A., Janssen, O. E., Hahn, S., Lahner, H., Dietz, T. et al. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS). BMC Med. Genet. 11, 12 (2010
28. Cho, Y. S., Go, M. J., Kim, Y. J., Heo, J. Y., Oh, J. H., Ban, H. J. et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat. Genet. 41, 527-534 (2009
29. Devlin, B., Roeder, K. & Wasserman, L. Genomic control, a new approach to geneticbased association studies. Theor. Popul. Biol. 60, 155-166 (2001
30. Barber, T. M., McCarthy, M. I., Wass, J. A. & Franks, S. Obesity and polycystic ovary syndrome. Clin. Endocrinol. 65, 137-145 (2006
31. Pasquali, R., Casimirri, F. & Vicennati, V. Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Hum. Reprod. 12(Suppl 1), 82-87 (1997
32. Ozcan, U., Cao, Q., Yilmaz, E., Lee, A. H., Iwakoshi, N. N., Ozdelen, E. et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457-461 (2004
33. Sharma, N. K., Das, S. K., Mondal, A. K., Hackney, O. G., Chu, W. S., Kern, P. A. et al. Endoplasmic reticulum stress markers are associated with obesity in nondiabetic subjects. J. Clin. Endocrinol. Metab. 93, 4532-4541 (2008
34. Han, A. R., Kim, H. O., Cha, S. W., Park, C. W., Kim, J. Y., Yang, K. M. et al. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: A case-control study. Clin. Exp. Reprod.Med. 38, 103-108 (2011
35. Palomba, S., Falbo, A., Russo, T., Rivoli, L., Orio, M., Cosco, A. G. et al. The risk of a persistent glucose metabolism impairment after gestational diabetes mellitus is increased in patients with polycystic ovary syndrome. Diabetes Care 35, 861-867 (2012
36. Dmitrovic, R., Katcher, H. I., Kunselman, A. R. & Legro, R. S. Continuous glucose monitoring during pregnancy in women with polycystic ovary syndrome. Obstet. Gynecol. 118, 878-885 (2012
37. Kjerulff, L. E., Sanchez-Ramos, L. & Duffy, D. Pregnancy outcomes in women with polycystic ovary syndrome: A metaanalysis. Am. J. Obstet. Gynecol. 204, 558. e551-556 (2011
38. Huo, J., Xu, S. & Lam, K. P. Fas apoptosis inhibitory molecule regulates T cell receptormediated apoptosis of thymocytes by modulating Akt activation and Nur77 expression. J. Biol. Chem. 285, 11827-11835 (2010
39. Soggia, A. P., Correa-Giannella, M. L., Fortes, M. A., Luna, A. M. & Pereira, M. A. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. BMC Med. Genet. 11, 3 (2010
40. Morton, N. M., Nelson, Y. B., Michailidou, Z., Di Rollo, E. M., Ramage, L., Hadoke, P. W. et al. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. PLoS One 6, e23944 (2011
41. Li, T., Zhao, H., Zhao, X., Zhang, B., Cui, L., Shi, Y. et al. Identification of YAP1 as a novel susceptibility gene for polycystic ovary syndrome. J. Med. Genet. 49, 254-257 (2012
42. Goodarzi, M. O., Louwers, Y. V., Taylor, K. D., Jones, M. R., Cui, J., Kwon, S. et al. Replication of association of a novel insulin receptor gene polymorphism with polycystic ovary syndrome. Fertil. Steril. 95, 1736-1741. e1-11 (2011)