Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia
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DOI：
10.1038/ng0613-712b
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发表时间：
2013-05
期刊：
Nature Genetics
影响因子：
30.8
通讯作者：
V. Verhoeven;P. Hysi;R. Wojciechowski;Q. Fan;J. Guggenheim;René Höhn;S. Macgregor;A. Hewitt;A. Nag;Ching-Yu Cheng;Ekaterina Yonova-Doing;Xin Zhou;M. Ikram;Gabriëlle H S Buitendijk;George Mcmahon;J. Kemp;B. S. Pourcain;Claire L. Simpson;Kari-Matti Mäkelä;T. Lehtimäki;M. Kähönen;A. Paterson;S. M. Hosseini;H. Wong;Liang Xu;J. Jonas;O. Pärssinen;J. Wedenoja;S. Yip;Daniel W. H. Ho;C. Pang;L. J. Chen;K. Burdon;J. Craig;B. Klein;R. Klein;T. Haller;A. Metspalu;C. Khor;E. Tai;T. Aung;E. Vithana;W. Tay;V. Barathi;Peng Chen;Ruoying Li;Jiemin Liao;Yingfeng Zheng;R. T. Ong;A. Döring;David M. Evans;N. Timpson;A. Verkerk;T. Meitinger;O. Raitakari;F. Hawthorne;T. Spector;L. Karssen;M. Pirastu;F. Murgia;W. Ang;A. Mishra;G. Montgomery;C. Pennell;P. Cumberland;I. Cotlarciuc;P. Mitchell;Jie-Jin Wang;M. Schache;Sarayut Janmahasatian;R. Igo;J. Lass;E. Chew;S. Iyengar;T. Gorgels;I. Rudan;C. Hayward;A. Wright;O. Polašek;Z. Vatavuk;James F. Wilson;B. Fleck;T. Zeller;A. Mirshahi;Christian Müller;A. Uitterlinden;F. Rivadeneira;J. Vingerling;A. Hofman;B. Oostra;N. Amin;A. Bergen;Y. Teo;J. Rahi;V. Vitart;Cathy Williams;P. Baird;T. Wong;K. Oexle;Aharon Wegner;N. Pfeiffer;D. Mackey;T. Young;C. Duijn;S. Saw;J. Bailey-Wilson;D. Stambolian;C. Klaver;C. Hammond
V. Verhoeven;P. Hysi;R. Wojciechowski;Q. Fan;J. Guggenheim;René Höhn;S. Macgregor;A. Hewitt;A. Nag;Ching-Yu Cheng;Ekaterina Yonova-Doing;Xin Zhou;M. Ikram;Gabriëlle H S Buitendijk;George Mcmahon;J. Kemp;B. S. Pourcain;Claire L. Simpson;Kari-Matti Mäkelä;T. Lehtimäki;M. Kähönen;A. Paterson;S. M. Hosseini;H. Wong;Liang Xu;J. Jonas;O. Pärssinen;J. Wedenoja;S. Yip;Daniel W. H. Ho;C. Pang;L. J. Chen;K. Burdon;J. Craig;B. Klein;R. Klein;T. Haller;A. Metspalu;C. Khor;E. Tai;T. Aung;E. Vithana;W. Tay;V. Barathi;Peng Chen;Ruoying Li;Jiemin Liao;Yingfeng Zheng;R. T. Ong;A. Döring;David M. Evans;N. Timpson;A. Verkerk;T. Meitinger;O. Raitakari;F. Hawthorne;T. Spector;L. Karssen;M. Pirastu;F. Murgia;W. Ang;A. Mishra;G. Montgomery;C. Pennell;P. Cumberland;I. Cotlarciuc;P. Mitchell;Jie-Jin Wang;M. Schache;Sarayut Janmahasatian;R. Igo;J. Lass;E. Chew;S. Iyengar;T. Gorgels;I. Rudan;C. Hayward;A. Wright;O. Polašek;Z. Vatavuk;James F. Wilson;B. Fleck;T. Zeller;A. Mirshahi;Christian Müller;A. Uitterlinden;F. Rivadeneira;J. Vingerling;A. Hofman;B. Oostra;N. Amin;A. Bergen;Y. Teo;J. Rahi;V. Vitart;Cathy Williams;P. Baird;T. Wong;K. Oexle;Aharon Wegner;N. Pfeiffer;D. Mackey;T. Young;C. Duijn;S. Saw;J. Bailey-Wilson;D. Stambolian;C. Klaver;C. Hammond
中科院分区：
生物学1区
文献类型：
--
作者：
V. Verhoeven;P. Hysi;R. Wojciechowski;Q. Fan;J. Guggenheim;René Höhn;S. Macgregor;A. Hewitt;A. Nag;Ching-Yu Cheng;Ekaterina Yonova-Doing;Xin Zhou;M. Ikram;Gabriëlle H S Buitendijk;George Mcmahon;J. Kemp;B. S. Pourcain;Claire L. Simpson;Kari-Matti Mäkelä;T. Lehtimäki;M. Kähönen;A. Paterson;S. M. Hosseini;H. Wong;Liang Xu;J. Jonas;O. Pärssinen;J. Wedenoja;S. Yip;Daniel W. H. Ho;C. Pang;L. J. Chen;K. Burdon;J. Craig;B. Klein;R. Klein;T. Haller;A. Metspalu;C. Khor;E. Tai;T. Aung;E. Vithana;W. Tay;V. Barathi;Peng Chen;Ruoying Li;Jiemin Liao;Yingfeng Zheng;R. T. Ong;A. Döring;David M. Evans;N. Timpson;A. Verkerk;T. Meitinger;O. Raitakari;F. Hawthorne;T. Spector;L. Karssen;M. Pirastu;F. Murgia;W. Ang;A. Mishra;G. Montgomery;C. Pennell;P. Cumberland;I. Cotlarciuc;P. Mitchell;Jie-Jin Wang;M. Schache;Sarayut Janmahasatian;R. Igo;J. Lass;E. Chew;S. Iyengar;T. Gorgels;I. Rudan;C. Hayward;A. Wright;O. Polašek;Z. Vatavuk;James F. Wilson;B. Fleck;T. Zeller;A. Mirshahi;Christian Müller;A. Uitterlinden;F. Rivadeneira;J. Vingerling;A. Hofman;B. Oostra;N. Amin;A. Bergen;Y. Teo;J. Rahi;V. Vitart;Cathy Williams;P. Baird;T. Wong;K. Oexle;Aharon Wegner;N. Pfeiffer;D. Mackey;T. Young;C. Duijn;S. Saw;J. Bailey-Wilson;D. Stambolian;C. Klaver;C. Hammond

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屈光不正是世界范围内最常见的眼部疾病，也是失明的主要原因。近视影响超过30%的西方人口和高达80%的亚洲人。CREAM联盟进行了全基因组荟萃分析，包括来自27项欧洲血统研究的37,382名个体和来自5个亚洲队列的8,376名个体。我们在欧洲血统的个体中发现了16个新的屈光不正位点，其中8个与亚洲人相同。联合分析确定了8个额外的相关位点。新发现的基因位点包括神经传递（GRIA 4）、离子转运（KCNQ 5）、视黄酸代谢（RDH 5）、细胞外基质重塑（LAMA 2和BMP 2）和眼发育（SIX 6和PRSS 56）的候选基因。我们还证实了先前报道的与GJD 2和RASGRF 1的关联。使用相关SNPs的风险评分分析显示，携带最高遗传负荷的个体患近视的风险增加了10倍。我们的研究结果是基于对独立多血统研究的大型荟萃分析，大大促进了对屈光不正和近视相关机制的理解。
Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2andBMP2) and eye development (SIX6andPRSS56). We also confirmed previously reported associations withGJD2andRASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.