Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts.
Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts.
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DOI：
10.1136/jmedgenet-2011-100427
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发表时间：
2012-02
影响因子：
4
通讯作者：
Urbanek M
中科院分区：
文献类型：
--
作者：
Goodarzi MO;Jones MR;Li X;Chua AK;Garcia OA;Chen YD;Krauss RM;Rotter JI;Ankener W;Legro RS;Azziz R;Strauss JF 3rd;Dunaif A;Urbanek M
多囊卵巢综合征（PCOS）是一种复杂的内分泌疾病，具有很强的家族性。多囊卵巢综合征的特征是高雄激素血症和月经不调。最近一项在中国人群中进行的PCOS全基因组关联研究确定了三个可重复的PCOS易感基因座，分别定位于2p16.3（促黄体激素/绒毛膜促性腺激素受体; LHCGR）、2 p21（甲状腺相关蛋白; THADA）和9q33.3（DENN/MADD结构域包含1A; DENDIA）。这些基因座在非中国PCOS人群中的影响仍有待确定。我们在两个欧洲来源的PCOS队列（队列A = 939例病例和957例对照;队列B = 535例病例和845例对照）中检测了与中国PCOS三个基因座相关的7个单核苷酸多态性与PCOS的相关性。病例符合NICHD PCOS诊断标准。在我们的队列中，DEND 1A的变异与PCOS密切相关（pcombined cohort =10−8）; THADA的多种变异也与PCOS相关，而LHCGR变异与PCOS相关性没有显著证据。我们具有大于80%的功效来检测与Chen等人对DENND 1A和THADA观察到的相似大小的效应，但在p=0.0001时，LHCGR的功效降低（<40%）。在p=0.01时，我们对LHCGR有足够的把握度（57-88%）。在中国PCOS GWAS中鉴定的至少两个PCOS易感基因座（DEND 1A和THADA）也与欧洲来源人群中的PCOS相关，因此可能在PCOS的病因学中很重要，无论种族如何。我们对LHCGR基因的分析不足以检测到适度的影响。
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with a strong familial component. PCOS is characterized by hyperandrogenemia and irregular menses. A recent genome wide association study of PCOS in a Chinese cohort identified three reproducible PCOS susceptibility loci mapping to 2p16.3 (luteinizing hormone/choriogonadotropin receptor; LHCGR), 2p21 (thyroid associated protein; THADA), and 9q33.3 (DENN/MADD domain containing 1A; DENNDIA). The impact of these loci in non-Chinese PCOS cohorts remains to be determined. We tested association with PCOS of seven single nucleotide polymorphisms mapping to the three Chinese PCOS loci in two European-derived PCOS cohorts (Cohort A = 939 cases and 957 controls; Cohort B = 535 cases and 845 controls). Cases fulfilled the NICHD criteria for PCOS. Variation in DENND1A was strongly associated with PCOS in our cohort (pcombined cohorts=10−8 ); multiple variants in THADA were also associated with PCOS, while there was no significant evidence for association of LHCGR variation with PCOS. We had greater than 80% power to detect an effect of similar size as was observed by Chen et al. for DENND1A and THADA but reduced power (at <40%) for LHCGR at p=0.0001. We had sufficient power (57-88%) for LHCGR at p=0.01. At least two of the PCOS susceptibility loci identified in the Chinese PCOS GWAS (DENND1A and THADA) are also associated with PCOS in European-derived populations, and therefore likely to be important in the etiology of PCOS regardless of ethnicity. Our analysis of the LHCGR gene was not sufficiently powered to detect modest effects.
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影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
DOI：
10.1073/pnas.0602025103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Sam, S;Legro, RS;Dunaif, A
通讯作者：
Dunaif, A
影响因子：
5.8
作者：
Urbanek, M;Woodroffe, A;Spielman, RS
通讯作者：
Spielman, RS
影响因子：
6.1
作者：
Fauser, BCJM;Chang, J;Lobo, R
通讯作者：
Lobo, R
影响因子：
6.7
作者：
Azziz, Ricardo;Dumesic, Daniel A.;Goodarzi, Mark O.
通讯作者：
Goodarzi, Mark O.