A genome-wide association study for susceptibility to myopia identifies PIK3CG-PRKAR2B locus and lipid metabolism.

Myopia (shortsightedness) is a leading cause of visual impairment worldwide. Its prevalence reaches 80-90% in some Asian populations while it is much lower in Western populations. Myopia is complex disease with contribution from environmental and genetic factors as well as their interactions. Time spent outdoors and years spent in education are risk factors. Recent genome-wide association studies (GWAS) have also identified numerous common genetic variants associated with refractive error and myopia. Understandably, the interactions between environmental and genetic factors are much less studied in human cohorts.
To identify gene-environment interactions conferring susceptibility to myopia, a GWAS was performed in chicks whose vision was monocularly deprived by putting a diffuser over one eye. One locus encompassing the genes PIK3CG and PRKAR2B was found genome-wide significant after Bonferroni adjustment. The results were validated with three large human cohorts. To search for independent evidence of a role for the PI3K signalling pathway in refractive development, we also used multivariable Mendelian randomization to assess the causal role of lipids. This work identifies the PIK3CG-PRKAR2B locus as a mediator of susceptibility to environmentally induced myopia in a well-established animal model, and confirms a role for PI3K signalling pathway in conferring susceptibility to myopia in three independent human cohorts.

Prof. Yip is a professor in the Department of Health Technology and Informatics, The Hong Kong Polytechnic University. He took up the Headship of the Department in January 2016. He obtained his PhD in Human Genetics from University College London in 1997. His research interests focus on genetic variations – their detection, application and significance in relation to human health-related conditions. In particular, his current projects revolve around (a) genomics of ocular diseases (e.g. myopia), (b) molecular genetics of blood cancers and© molecular diagnostics. His on-going work investigates the functional effects of genetic variants identified in GWAS. He collaborates with researchers from local and overseas universities and a large research consortium (Consortium for Refractive Errors and Myopia, CREAM). He has published over 100 peer-reviewed papers.