A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
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DOI：
10.1038/ng.3226
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发表时间：
2015-04
期刊：
影响因子：
30.8
通讯作者：
Khor CC
中科院分区：
文献类型：
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作者：
Aung T;Ozaki M;Mizoguchi T;Allingham RR;Li Z;Haripriya A;Nakano S;Uebe S;Harder JM;Chan AS;Lee MC;Burdon KP;Astakhov YS;Abu-Amero KK;Zenteno JC;Nilgün Y;Zarnowski T;Pakravan M;Safieh LA;Jia L;Wang YX;Williams S;Paoli D;Schlottmann PG;Huang L;Sim KS;Foo JN;Nakano M;Ikeda Y;Kumar RS;Ueno M;Manabe S;Hayashi K;Kazama S;Ideta R;Mori Y;Miyata K;Sugiyama K;Higashide T;Chihara E;Inoue K;Ishiko S;Yoshida A;Yanagi M;Kiuchi Y;Aihara M;Ohashi T;Sakurai T;Sugimoto T;Chuman H;Matsuda F;Yamashiro K;Gotoh N;Miyake M;Astakhov SY;Osman EA;Al-Obeidan SA;Owaidhah O;Al-Jasim L;Al Shahwan S;Fogarty RA;Leo P;Yetkin Y;Oğuz Ç;Kanavi MR;Beni AN;Yazdani S;Akopov EL;Toh KY;Howell GR;Orr AC;Goh Y;Meah WY;Peh SQ;Kosior-Jarecka E;Lukasik U;Krumbiegel M;Vithana EN;Wong TY;Liu Y;Koch AE;Challa P;Rautenbach RM;Mackey DA;Hewitt AW;Mitchell P;Wang JJ;Ziskind A;Carmichael T;Ramakrishnan R;Narendran K;Venkatesh R;Vijayan S;Zhao P;Chen X;Guadarrama-Vallejo D;Cheng CY;Perera SA;Husain R;Ho SL;Welge-Luessen UC;Mardin C;Schloetzer-Schrehardt U;Hillmer AM;Herms S;Moebus S;Nöthen MM;Weisschuh N;Shetty R;Ghosh A;Teo YY;Brown MA;Lischinsky I;Blue Mountains Eye Study GWAS Team;Wellcome Trust Case Control Consortium 2;Crowston JG;Coote M;Zhao B;Sang J;Zhang N;You Q;Vysochinskaya V;Founti P;Chatzikyriakidou A;Lambropoulos A;Anastasopoulos E;Coleman AL;Wilson MR;Rhee DJ;Kang JH;May-Bolchakova I;Heegaard S;Mori K;Alward WL;Jonas JB;Xu L;Liebmann JM;Chowbay B;Schaeffeler E;Schwab M;Lerner F;Wang N;Yang Z;Frezzotti P;Kinoshita S;Fingert JH;Inatani M;Tashiro K;Reis A;Edward DP;Pasquale LR;Kubota T;Wiggs JL;Pasutto F;Topouzis F;Dubina M;Craig JE;Yoshimura N;Sundaresan P;John SW;Ritch R;Hauser MA;Khor CC
剥脱综合征（XFS）是开角型青光眼最常见的病因。为了更好地了解XFS的病因，我们对来自日本的1,484名患者和1,188名对照进行了全基因组关联研究（GWAS），并对来自6大洲17个国家的6,901名患者和20,727名对照进行了最重要的研究结果。我们发现一个新的基因座（CACNA1A rs4926244）与XFS易感性增加之间存在显著关联（优势比[OR] = 1.16, P = 3.36 × 10−11）。虽然证实了LOXL1位点的压倒性关联，但关键SNP标记（LOXL1 rs4886776）显示出等位基因逆转依赖于族群（日本人：ora等位基因= 9.87,P = 2.13 × 10−217；非日本人：ora等位基因= 0.49,P = 2.35 × 10−31）。我们的研究结果代表了LOXL1以外的第一个遗传位点，其对XFS的意义超过了全基因组意义，并为该疾病的生物学和发病机制提供了见解。
Exfoliation syndrome (XFS) is the commonest recognizable cause of open angle glaucoma world-wide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) on 1,484 patients and 1,188 controls from Japan, and followed up the most significant findings on a further 6,901 patients and 20,727 controls from 17 countries across 6 continents. We discovered a significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (Odds ratio [OR] = 1.16, P = 3.36 × 10−11). Although overwhelming association at the LOXL1 locus was confirmed, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on ethnic grouping (In Japanese: ORA-allele= 9.87, P = 2.13 × 10−217; In non-Japanese: ORA-allele= 0.49, P = 2.35 × 10−31). Our findings represent the first genetic locus outside of LOXL1 which surpasses genome-wide significance for XFS, and provides insight into the biology and pathogenesis of the disease.