Dataset Information

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

ABSTRACT: 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 (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. 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.

SUBMITTER: Verhoeven VJ

PROVIDER: S-EPMC3740568 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Verhoeven Virginie J M VJ Hysi Pirro G PG Wojciechowski Robert R Fan Qiao Q Guggenheim Jeremy A JA Höhn René R MacGregor Stuart S Hewitt Alex W AW Nag Abhishek A Cheng Ching-Yu CY Yonova-Doing Ekaterina E Zhou Xin X Ikram M Kamran MK Buitendijk Gabriëlle H S GH McMahon George G Kemp John P JP Pourcain Beate St BS Simpson Claire L CL Mäkelä Kari-Matti KM Lehtimäki Terho T Kähönen Mika M Paterson Andrew D AD Hosseini S Mohsen SM Wong Hoi Suen HS Xu Liang L Jonas Jost B JB Pärssinen Olavi O Wedenoja Juho J Yip Shea Ping SP Ho Daniel W H DW Pang Chi Pui CP Chen Li Jia LJ Burdon Kathryn P KP Craig Jamie E JE Klein Barbara E K BE Klein Ronald R Haller Toomas T Metspalu Andres A Khor Chiea-Chuen CC Tai E-Shyong ES Aung Tin T Vithana Eranga E Tay Wan-Ting WT Barathi Veluchamy A VA Chen Peng P Li Ruoying R Liao Jiemin J Zheng Yingfeng Y Ong Rick T RT Döring Angela A Evans David M DM Timpson Nicholas J NJ Verkerk Annemieke J M H AJ Meitinger Thomas T Raitakari Olli O Hawthorne Felicia F Spector Tim D TD Karssen Lennart C LC Pirastu Mario M Murgia Federico F Ang Wei W Mishra Aniket A Montgomery Grant W GW Pennell Craig E CE Cumberland Phillippa M PM Cotlarciuc Ioana I Mitchell Paul P Wang Jie Jin JJ Schache Maria M Janmahasatian Sarayut S Igo Robert P RP Lass Jonathan H JH Chew Emily E Iyengar Sudha K SK Gorgels Theo G M F TG Rudan Igor I Hayward Caroline C Wright Alan F AF Polasek Ozren O Vatavuk Zoran Z Wilson James F JF Fleck Brian B Zeller Tanja T Mirshahi Alireza A Müller Christian C Uitterlinden André G AG Rivadeneira Fernando F Vingerling Johannes R JR Hofman Albert A Oostra Ben A BA Amin Najaf N Bergen Arthur A B AA Teo Yik-Ying YY Rahi Jugnoo S JS Vitart Veronique V Williams Cathy C Baird Paul N PN Wong Tien-Yin TY Oexle Konrad K Pfeiffer Norbert N Mackey David A DA Young Terri L TL van Duijn Cornelia M CM Saw Seang-Mei SM Bailey-Wilson Joan E JE Stambolian Dwight D Klaver Caroline C CC Hammond Christopher J CJ

Nature genetics 20130210 3

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 l ...[more]

PMID: 23396134

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Project description:Myopia is the most common ocular disease worldwide. We investigated the association of high myopia with the common single nucleotide polymorphisms (SNPs) of five candidate genes - early growth response 1 (EGR1), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS), jun oncogene (JUN), vasoactive intestinal peptide (VIP), and vasoactive intestinal peptide receptor 2 (VIPR2). We recruited 1200 unrelated Chinese subjects with 600 cases (spherical equivalent ?-8.00 diopters) and 600 controls (spherical equivalent within ±1.00 diopter). A discovery sample set was formed from 300 cases and 300 controls, and a replication sample set from the remaining samples. Tag SNPs were genotyped for the discovery sample set, and the most significant haplotypes and their constituent SNPs were followed up with the replication sample set. The allele and haplotype frequencies in cases and controls were compared by logistic regression adjusted for sex and age to give P a values, and multiple comparisons were corrected by permutation test to give P aemp values. Odd ratios (OR) were calculated accordingly. In the discovery phase, EGR1, JUN and VIP did not show any significant association while FOS and VIPR2 demonstrated significant haplotype association with high myopia. In the replication phase, the haplotype association for VIPR2 was successfully replicated, but not FOS. In analysis combining both sample sets, the most significant association signals of VIPR2 were the single marker rs2071625 (P a?=?0.0008, P aemp?=?0.0046 and OR?=?0.75) and the 4-SNP haplotype window rs2071623-rs2071625-rs2730220-rs885863 (omnibus test, P a?=?9.10e-10 and P aemp?=?0.0001) with one protective haplotype (GGGG: P aemp?=?0.0002 and OR?=?0.52) and one high-risk haplotype (GAGA: P aemp?=?0.0027 and OR?=?4.68). This 4-SNP haplotype window was the most significant in all sample sets examined. This is the first study to suggest a role of VIPR2 in the genetic susceptibility to high myopia. EGR1, JUN, FOS and VIP are unlikely to be important in predisposing humans to high myopia.

Dataset Information

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

Publications

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

Similar Datasets

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