Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error
Fan Q., Verhoeven VJM., Wojciechowski R., Barathi VA., Hysi PG., Guggenheim JA., Höhn R., Vitart V., Khawaja AP., Yamashiro K., Hosseini SM., Lehtimäki T., Lu Y., Haller T., Xie J., Delcourt C., Pirastu M., Wedenoja J., Gharahkhani P., Venturini C., Miyake M., Hewitt AW., Guo X., Mazur J., Huffman JE., Williams KM., Polasek O., Campbell H., Rudan I., Vatavuk Z., Wilson JF., Joshi PK., McMahon G., St Pourcain B., Evans DM., Simpson CL., Schwantes-An T-H., Igo RP., Mirshahi A., Cougnard-Gregoire A., Bellenguez C., Blettner M., Raitakari O., Kähönen M., Seppälä I., Zeller T., Meitinger T., Ried JS., Gieger C., Portas L., van Leeuwen EM., Amin N., Uitterlinden AG., Rivadeneira F., Hofman A., Vingerling JR., Wang YX., Wang X., Tai-Hui Boh E., Ikram MK., Sabanayagam C., Gupta P., Tan V., Zhou L., Ho CEH., Lim W., Beuerman RW., Siantar R., Tai E-S., Vithana E., Mihailov E., Khor C-C., Hayward C., Luben RN., Foster PJ., Klein BEK., Klein R., Wong H-S., Mitchell P., Metspalu A., Aung T., Young TL., He M., Pärssinen O., van Duijn CM., Jin Wang J., Williams C., Jonas JB., Teo Y-Y., Mackey DA., Oexle K., Yoshimura N., Paterson AD., Pfeiffer N., Wong T-Y., Baird PN., Stambolian D., Wilson JEB., Cheng C-Y., Hammond CJ., Klaver CCW., Saw S-M., Rahi JS., Korobelnik J-F., Kemp JP., Timpson NJ., Smith GD., Craig JE., Burdon KP., Fogarty RD., Iyengar SK., Chew E., Janmahasatian S., Martin NG., MacGregor S., Xu L., Schache M., Nangia V., Panda-Jonas S., Wright AF., Fondran JR., Lass JH., Feng S., Zhao JH., Khaw K-T., Wareham NJ., Rantanen T., Kaprio J., Pang CP., Chen LJ., Tam PO., Jhanji V., Young AL., Döring A., Raffel LJ., Cotch M-F., Li X., Yip SP., Yap MKH., Biino G., Vaccargiu S., Fossarello M., Fleck B., Yazar S., Tideman JWL., Tedja M., Deangelis MM., Morrison M., Farrer L., Zhou X., Chen W., Mizuki N., Meguro A., Mäkelä KM.
AbstractMyopia 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.