一項全基因組關聯(lián)研究確定了三種與芬蘭和愛沙尼亞女性多囊*巢綜合征(PCOS)風險增加相關的遺傳變異。

　　確定的這些變體中的兩個影響CHEK2基因。CHEK2是一種已知在細胞質(zhì)量控制和受損DNA修復中發(fā)揮關鍵作用的基因，這也與*巢儲備和更年期年齡差異有關。

　　“這種技術的遺傳物質(zhì)（DNA）序列在PCOS患者進行比較，例如，對婦女沒有條件，并允許它們與感興趣的性狀的組中更加頻繁序列的變化的標識，”所述Triin Laisk博士，愛沙尼亞塔爾圖大學基因組學研究所副教授。

　　該研究由塔爾圖大學和芬蘭奧盧大學的研究人員進行，分析了超過233,000名女性的基因數(shù)據(jù)。從國家登記冊中總共確定了3609例PCOS病例，所有其他229,788名女性被指定為對照。首先使用來自FinnGen研究的141,355名女性的數(shù)據(jù)進行了全基因組關聯(lián)研究，然后使用來自愛沙尼亞生物庫的92,042名女性的單獨數(shù)據(jù)集驗證了這些發(fā)現(xiàn)。

　　發(fā)表在《人類生殖》雜志上的研究結果包括CHEK2基因中的兩種因果變異和MYO10X基因中的一種。

　　之前的研究發(fā)現(xiàn)了與PCOS相關的其他基因。然而，這項研究的作者認為，使用特定人群的數(shù)據(jù)可以幫助提供進一步的見解。

　　作者指出，芬蘭人口中有大量遺傳變異，這些變異在歐洲其他地區(qū)以低頻率發(fā)生。愛沙尼亞人口被認為在基因上與芬蘭人口最接近。

　　“由于人口歷史的差異，芬蘭和愛沙尼亞人群中某些變異的富集提供了一個獨特的機會，當只關注這些人群時，可以捕獲與PCOS相關的新型罕見遺傳變異，”博士生、共同第一人Natàlia Pujol Gualdo說。該研究的作者。

　　“需要進一步的研究來探索CHEK2變異在PCOS中的作用，我們希望這項研究可以作為進一步實驗的基礎，以闡明它們之間的相互作用，”Laisk博士說?！芭c此同時，這項研究強調(diào)了針對特定人群的生物庫計劃作為探索復雜疾病遺傳景觀的獨特手段的重要性”。

　　目前尚不清楚這些遺傳變異是否會在其他種族中發(fā)現(xiàn)，但它們有助于我們?nèi)媪私釶COS的遺傳控制。

　　A genome-wide association study has identified three genetic variants associated with increased risk of polycystic ovary syndrome(PCOS)in Finnish and Estonian women.

　　Two of these variants identified affect the CHEK2 gene.CHEK2 is a gene known to play a key role in cell quality control and the repair of damaged DNA that has also been linked to ovarian reserve and differences at age of menopause.

　　'This technique compares the genetic material(DNA)sequence in women with PCOS,for instance,to women without the condition and allows the identification of sequence changes which are more frequent in the group with the trait of interest,'said Dr Triin Laisk,associate professor at the Institute of Genomics at the University of Tartu in Estonia.

　　Conducted by researchers at University of Tartu and the University of Oulu in Finland,the study analysed the genetic data of over 233,000 women.A total of 3609 PCOS cases were identified from national registers with all other 229,788 women designated controls.First a genome wide association study was carried out using data on 141,355 women from the FinnGen study,and then these findings were validated using a separate dataset of 92,042 women from the Estonian biobank.

　　Published in the journal Human Reproduction,the findings included two causal variants in the CHEK2 gene and one on the MYO10X gene.

　　Previous research has discovered other genes associated with PCOS.The authors of this study believe however that using population-specific data could help provide further insights.

　　The Finnish population has a high number of genetic variants that occur at a low frequency across the rest of Europe,the authors note.The Estonian population is thought to be genetically closest to the Finnish population.

　　'Due to differences in demographic history,the enrichment of some variants in Finnish and Estonian populations provided a unique opportunity to capture novel rare genetic variants associated with PCOS when focusing only on these populations,'said Natàlia Pujol Gualdo,PhD student and co-first author of the study.

　　'Further research is needed to explore the role of CHEK2 variation in PCOS and we hope this study serves as a base for further experiments that can clarify their interplay,'said Dr Laisk.'At the same time,this study highlights the importance of population-specific biobank initiatives as unique means to seek into the genetic landscape of complex diseases'.

　　It is not yet known whether these genetic variants will be found in other ethnic groups,but they contribute to our overall understanding of the genetic control of PCOS.