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

Hwang, Joo Yeon; Lee, Eun Ju; Go, Min Jin; Sung, Yeon Ah; Lee, Hye Jin; Kwak, Soo Heon; Jang, Hak Chul; Park, Kyong Soo; Lee, Hye Ja; Jang, Han Byul; Song, Jihyun; Park, Kyung Hee; Kim, Hyung Lae; Cho, Myeong Chan; Lee, Jong‐Young

doi:10.1038/jhg.2012.92

Cited by 56 publications

(28 citation statements)

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“…A GWAS study conducted by a Korean group failed to confirm these results and found that only the glycogen synthase 2 (GYS2) gene could be linked to PCOS and its metabolic complications (Hwang et al 2012). Another GWAS study conducted in the USA that analysed genes that code for proteins associated with metabolic and cardiovascular abnormalities also did not demonstrate a hereditary component of PCOS .…”

Section: Genetic Factors Associated With Pcosmentioning

confidence: 87%

“…Because there are three supported definitions of PCOS (Zawadski & Dunaif 1992, Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004, Azziz et al 2006), comparing the results reported in different publications is somewhat difficult. Whereas some authors use a PCOS diagnosis based on criteria listed by the National Institutes of Health (NIH) (Goodarzi et al 2012, Welt et al 2012, Hwang et al 2012, Mutharasan et al 2013, others use the criteria proposed by the American Society of Human Reproduction/European Society of Human Reproduction and Embryology (Chen et al 2011, Shi et al 2012, Hwang et al 2012, Louwers et al 2013, which thereby intensifies discrepancies in the published work on the genetic analysis of PCOS. Some authors have not even attempted to standardise the diagnosis of PCOS (Davies et al 2012, Hizli et al 2012, and they include in their studies women with polycystic ovaries on ultrasonography only, a finding that alone does not increase the risk for PCOS-associated conditions (Cresswell et al 1997), or they collect retrospective data from medical records that antedate the publication of the first consensus on PCOS by the NIH (Mumm et al 2013).…”

mentioning

confidence: 94%

“…Because the cardio-metabolic profile of PCOS phenotypes characterised by hyperandrogenism and chronic anovulation is poorer, the inclusion of nonhyperandrogenic phenotypes might favour the occurrence of bias in the assessment of the aetiopathogenesis of PCOS and its relationship to cardiovascular comorbidities during late stages of life (Melo et al 2011, Daan et al 2014. Moreover, most of the existing studies are multicentre cross-sectional or case-control studies in which women at different stages of life and who have a varied prevalence of comorbidities associated with PCOS were analysed (Michelmore et al 2001, Ibáñ ez et al 2008, Legro et al 2010, Chen et al 2011, Hizli et al 2012, Hwang et al 2012, Shi et al 2012, Louwers et al 2013, Shayeb et al 2014.…”

mentioning

confidence: 99%

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Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

Melo¹,

Dias²,

Cavalli³

et al. 2015

Reproduction

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Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intrauterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.Reproduction (2015) 150 R11-R24

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Section: Genetic Factors Associated With Pcosmentioning

confidence: 87%

mentioning

confidence: 94%

mentioning

confidence: 99%

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Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

Melo¹,

Dias²,

Cavalli³

et al. 2015

Reproduction

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show abstract

“…Epidemiológiai adatok alapján egyértelműen felvetődik a PCOS kialakulásában a genetikai faktorok szerepe [8][9][10][11][12][13][14][15][16]. Kutatások alapján látható, hogy monozigóta ikrekben a PCOS előfordulása kétszer gyakoribb, mint dizigótákban.…”

Section: Genetikai Faktorokunclassified

Genetikai és epigenetikai faktorok polycystás ovarium szindróma esetén

et al. 2016

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A polycystás ovarium szindróma kialakulásának pontos mechanizmusa a mai napig nem tisztázott, de környezeti, illetve genetikai tényezők nagy valószínűséggel szerepet játszhatnak a kialakulásában. Ezt a megállapítást alátámasztja a gyakran előforduló családi halmozódás is. A praenatalis időszakban elszenvedett teratogén hatások a postnatalis időszakban kialakuló krónikus betegségek kifejlődéséhez vezethetnek. A szerzők polycystás ovarium szindrómában a genetikai és epigenetikai tényezők szerepével foglalkozó, 2016. január 1-jéig publikált szakirodalmi közlemények alapján szakirodalmi kutatást végeztek. Jelen összefoglaló közlemény célja e különleges betegségcsoportra való figyelemfelhívás, valamint e kórképek genetikai és epigenetikai hátterének ismertetése. Orv. Hetil., 2016, 157(32), 1275-1281. Kulcsszavak: polycystás ovarium szindróma, genetika, epigenetika Genetic and epigenetic factors of polycystic ovary syndromeThe development of polycystic ovary syndrome and its exact pathophysiological mechanism is still unclear, but environmental and genetic factors likely play a role. Exposition to teratogenic effects during the prenatal development can lead to chronic diseases in the postnatal period. This finding confirms the common familial aggregation as well. A literature search was conducted up to January 1, 2016 for articles dealing with the genetic or epigenetic factors of polycystic ovary syndrome. This review will discuss the current understanding of the genetic basis and clinical presentation of this disease. Keywords: polycystic ovary syndrome, genetics, epigeneticsHerczeg, Z., Vanya, M., Szili, K., Dézsi, Cs., Nagy, Zs., Szabó, J. [Genetic and epigenetic factors of polycystic ovary syndrome]. Orv. Hetil., 2016, 157(32), 1275-1281. Rövidítések ACTH = adrenokortikotrop hormon; AEPCOS = Androgen Excess and PCOS Society; AR = androgénreceptor; CAG repeat = citozin-adenin-guanin ismétlődés; FSH = folliculus stimulating hormone; FTO = alpha-ketoglutarate-dependent dioxygenase; GnRH = gonadotropin releasing hormone; GWAS = genome-wide association studies; INSR = inzulinreceptor-gén; LH = luteinizáló hormon; NIH = National Institutes of Health; PCOS = polycystás ovarium szindróma; SHBG = szexhormonkötő globulin; SNP = single nucleotide polymorphism; SRDA = szteroid-5-α-reduktáz A polycystás ovárium szindróma (PCOS) definíciója a szindróma 1935-ös, Stein és Leventhal általi leírása óta a gyarapodó ismeretanyag ellenére a mai napig sem tisztá-zott. PrevalenciaA PCOS-t az egyik leggyakrabban előforduló endokrin betegségnek tartják a reproduktív korú nők körében [1][2][3]. Pontos előfordulási gyakoriságát nem egyszerű meg-

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“…to be associated with obesity, elevated testosterone levels, and the metabolic disturbance in PCOS patients [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS

Chen

Zhang

Zhao

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of the present study is to determine if paternal or maternal history of diabetes mellitus (DM) and hypertension (HT) contributes to the prevalence and phenotype of polycystic ovary syndrome (PCOS). Methods We performed an epidemiologic study about PCOS from four districts in Beijing, China, between 2008 and 2009. Parental histories of DM and HT were collected, and the basic characteristics and serum indices of 123 PCOS patients and 718 non-PCOS controls were tested. Results The prevalence of a parental history of DM and HT was significantly higher in PCOS patients than non-PCOS women (17.1 % vs. 9.2 % and 42.3 % vs. 26.0 %, P<0.05, respectively). When paternal history was separated from maternal history, only a paternal history of DM and HT reached statistical significance between PCOS and non-PCOS patients (odds ratio (OR)=3.42, 95 % confidence interval (CI)=1.69-6.91; OR=2.50, 95 % CI=1.58-3.93, respectively). A paternal history of both DM and HT was significantly associated with sex hormone-binding globulin, fasting plasma glucose, and fasting insulin levels, the free androgen index, and the homeostatic model assessment-insulin resistance in PCOS patients (P<0.05 for all). There was no independent association between maternal history and the clinical or biochemical phenotype of PCOS. Conclusions PCOS patients with a positive paternal history of both DM and HT have an adverse endocrine and metabolic profile. A paternal history of DM and HT poses a risk to PCOS.

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

Cited by 56 publications

References 42 publications

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

Genetikai és epigenetikai faktorok polycystás ovarium szindróma esetén

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS

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