Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
Bonnemaijer PWM., Leeuwen EMV., Iglesias AI., Gharahkhani P., Vitart V., Khawaja AP., Simcoe M., Höhn R., Cree AJ., Igo RP., Burdon KP., Craig JE., Hewitt AW., Jonas J., Khor C-C., Pasutto F., Mackey DA., Mitchell P., Mishra A., Pang C., Pasquale LR., Springelkamp H., Thorleifsson G., Thorsteinsdottir U., Viswanathan AC., Wojciechowski R., Wong T., Young TL., Zeller T., Allingham R., Budenz D., Bailey JC., Fingert J., Gaasterland D., Gaasterland T., Haines JL., Hark L., Hauser M., Kang JH., Kraft P., Lee R., Lichter P., Liu Y., Moroi S., Pasquale LR., Pericak M., Realini A., Rhee D., Richards JR., Ritch R., Scott WK., Singh K., Sit A., Vollrath D., Weinreb R., Wollstein G., Wilmer DZ., Atan D., Aslam T., Barman SA., Barrett JH., Bishop P., Blows P., Bunce C., Carare RO., Chakravarthy U., Chan M., Chua SYL., Crabb DP., Cumberland PM., Day A., Desai P., Dhillon B., Dick AD., Egan C., Ennis S., Foster P., Fruttiger M., Gallacher JEJ., Garway DF., Gibson J., Dan Gore None., Guggenheim JA., Hardcastle A., Harding SP., Hogg RE., Keane PA., Khaw PT., Lascaratos G., Macgillivray T., Mackie S., Martin K., McGaughey M., McGuinness B., McKay GJ., McKibbin M., Mitry D., Moore T., Morgan JE., Muthy ZA., O’Sullivan E., Owen CG., Patel P., Paterson E., Peto T., Petzold A., Rahi JS., Rudnikca AR., Self J., Sivaprasad S., Steel D., Stratton I., Strouthidis N., Sudlow C., Thomas D., Trucco E., Tufail A., Vernon SA., Viswanathan AC., Williams C., Williams K., Woodside JV., Yates MM., Yip J., Zheng Y., Gerhold-Ay A., Nickels S., Wilson JF., Hayward C., Boutin TS., Polašek O., Aung T., Khor CC., Amin N., Lotery AJ., Wiggs JL., Cheng C-Y., Hysi PG., Hammond CJ., Thiadens AAHJ., MacGregor S., Klaver CCW., Duijn CMV.
AbstractA new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.