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Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

ABSTRACT: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

SUBMITTER: Fan Q

PROVIDER: S-EPMC4820539 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

Fan Qiao Q Verhoeven Virginie J M VJ Wojciechowski Robert R Barathi Veluchamy A VA Hysi Pirro G PG Guggenheim Jeremy A JA Höhn René R Vitart Veronique V Khawaja Anthony P AP Yamashiro Kenji K Hosseini S Mohsen SM Lehtimäki Terho T Lu Yi Y Haller Toomas T Xie Jing J Delcourt Cécile C Pirastu Mario M Wedenoja Juho J Gharahkhani Puya P Venturini Cristina C Miyake Masahiro M Hewitt Alex W AW Guo Xiaobo X Mazur Johanna J Huffman Jenifer E JE Williams Katie M KM Polasek Ozren O Campbell Harry H Rudan Igor I Vatavuk Zoran Z Wilson James F JF Joshi Peter K PK McMahon George G St Pourcain Beate B Evans David M DM Simpson Claire L CL Schwantes-An Tae-Hwi TH Igo Robert P RP Mirshahi Alireza A Cougnard-Gregoire Audrey A Bellenguez Céline C Blettner Maria M Raitakari Olli O Kähönen Mika M Seppala Ilkka I Zeller Tanja T Meitinger Thomas T Ried Janina S JS Gieger Christian C Portas Laura L van Leeuwen Elisabeth M EM Amin Najaf N Uitterlinden André G AG Rivadeneira Fernando F Hofman Albert A Vingerling Johannes R JR Wang Ya Xing YX Wang Xu X Tai-Hui Boh Eileen E Ikram M Kamran MK Sabanayagam Charumathi C Gupta Preeti P Tan Vincent V Zhou Lei L Ho Candice E H CE Lim Wan'e W Beuerman Roger W RW Siantar Rosalynn R Tai E-Shyong ES Vithana Eranga E Mihailov Evelin E Khor Chiea-Chuen CC Hayward Caroline C Luben Robert N RN Foster Paul J PJ Klein Barbara E K BE Klein Ronald R Wong Hoi-Suen HS Mitchell Paul P Metspalu Andres A Aung Tin T Young Terri L TL He Mingguang M Pärssinen Olavi O van Duijn Cornelia M CM Jin Wang Jie J Williams Cathy C Jonas Jost B JB Teo Yik-Ying YY Mackey David A DA Oexle Konrad K Yoshimura Nagahisa N Paterson Andrew D AD Pfeiffer Norbert N Wong Tien-Yin TY Baird Paul N PN Stambolian Dwight D Wilson Joan E Bailey JE Cheng Ching-Yu CY Hammond Christopher J CJ Klaver Caroline C W CC Saw Seang-Mei SM Rahi Jugnoo S JS Korobelnik Jean-François JF Kemp John P JP Timpson Nicholas J NJ Smith George Davey GD Craig Jamie E JE Burdon Kathryn P KP Fogarty Rhys D RD Iyengar Sudha K SK Chew Emily E Janmahasatian Sarayut S Martin Nicholas G NG MacGregor Stuart S Xu Liang L Schache Maria M Nangia Vinay V Panda-Jonas Songhomitra S Wright Alan F AF Fondran Jeremy R JR Lass Jonathan H JH Feng Sheng S Zhao Jing Hua JH Khaw Kay-Tee KT Wareham Nick J NJ Rantanen Taina T Kaprio Jaakko J Pang Chi Pui CP Chen Li Jia LJ Tam Pancy O PO Jhanji Vishal V Young Alvin L AL Döring Angela A Raffel Leslie J LJ Cotch Mary-Frances MF Li Xiaohui X Yip Shea Ping SP Yap Maurice K H MK Biino Ginevra G Vaccargiu Simona S Fossarello Maurizio M Fleck Brian B Yazar Seyhan S Tideman Jan Willem L JW Tedja Milly M Deangelis Margaret M MM Morrison Margaux M Farrer Lindsay L Zhou Xiangtian X Chen Wei W Mizuki Nobuhisa N Meguro Akira A Mäkelä Kari Matti KM

Nature communications 20160329

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individ ...[more]

PMID: 27020472

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Project description:Accommodative esotropia (AE) is a convergent deviation due to an excess of the convergence linked to the innervational stimulus for accommodation and it is usually associated to the presence of hyperopia. The development of hyperopia over time has been widely described but the lack of comparative analysis among accommodative esotropia subtypes, does not allow to verify the existence of different developmental patterns. In this study we aimed to describe the long term changes of refractive error in patients affected by accommodative esotropia as a function of the strabismus type: refractive (RAE), non-refractive (NRAE) and partially accommodative esotropia (PAE). The medical records of 66 patients (24 RAE, 22 PAE, 20 NRAE), who wore the full correction of their cycloplegic refraction error during the entire follow up period, were retrospectively reviewed. Mean outcome was the analysis of the variations, among groups, of refractive error over time; differences between mild (≤3.00D) and high (≥5.00D) hyperopia, effects of amblyopia and relationship with AC/A ratio were also investigated. All patients were followed up from approximately 4 years of age to 20, with mean follow up of 16.06±0.29 years. Our results described similar non-linear trend of refractive error development among groups. The initial increase of hyperopia (up to 7-8 years) was followed by a decreasing trend persisting up to adulthood (approximately 20 years of age). During this period, spherical equivalent decreased at a lower mean annual rate in patients affected by RAE (-0.07D) compared to other groups (NRAE -0.11D, p = 0.003 and PAE 0.13D, p = 0.002). In all groups, however, significant amount of hyperopia was found at last examination; indeed the observed difference in SE values from baseline to the end of follow up, was not significant (RAE: +0.27D, 95% C.I. -0.49 to +1.04D, p = 0.472; PAE: -0.69D, 95% C.I. -1.67 to +0.28D, p = 0.154; NRAE: -0.39D, 95% C.I. -1.11 to +0.34D, p = 0.278). AC/A ratio, amblyopia and amount of initial hyperopia appeared to have no significant role in longitudinal change of the refractive error. In conclusion, this study provides a complete overview, from childhood to adulthood, of refractive error development in different form of accommodative esotropia.

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Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

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Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

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