title: FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome.
abstract: Dyslipidemia is common in polycystic ovary syndrome (PCOS). This study was aimed to investigate whether fatty acid desaturase genes (FADS), a dyslipidemia-related gene cluster, are associated with PCOS. We scanned variations of FADS genes using our previous data of genome-wide association study (GWAS) for PCOS and selected rs174570 for further study. The case-control study was conducted in an independent cohort of 1918 PCOS cases and 1889 age-matched controls and family-based study was conducted in a set of 243 core family trios with PCOS probands. Minor allele frequency (allele T) of rs174570 was significantly lower in PCOS cases than that in age-matched controls (P = 2.17E-03, OR = 0.85), even after adjustment of BMI and age. PCOS subjects carrying CC genotype had higher testosterone level and similar lipid/glucose level compared with those carrying TT or TC genotype. In trios, transmission disequilibrium test (TDT) analysis revealed risk allele C of rs174570 was significantly over-transmitted (P = 2.00E-04). Decreased expression of FADS2 was detected in PCOS cases and expression quantitative trait loci (eQTL) analysis revealed the risk allele C dosage was correlated with the decline of FADS2 expression (P = 0.002). Our results demonstrate that FADS1-FADS2 are susceptibility genes for PCOS.
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.|Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of joint and bone oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Tailai
authors.initials: T
authors.lastname: Chen
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Du
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Yingqian
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.|Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D005810:Multigene Family; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D012306:Risk; D055815:Young Adult
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D012333:RNA, Messenger; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human