Detection of adaptation to light environment in myopia-associated loci: Diversity of the myopia genetic background

The time spent outdoors and exposure to bright sunlight have been reported to play important roles in preventing myopia progression. Myopia prevalence is generally low in Europe, and we hypothesized that local adaptation of ancestors in insufficient sunlight regions might underlie this low prevalence in Europeans. To verify this conjecture and understand how ancestry adaptation influenced on the diversity of myopia genetic background, polygenic risk scores (PRS) was calculated and revealed that the genetic risk of myopia increased as latitude decreased in the 1000 genome projects (1KGP) EUR, and we further determined selection signatures near the rhodopsin (RHO) coding region in 1KGP Finnish. The derived allele frequencies of identified loci correlated with sunshine duration worldwide, and the allele age was estimated to be [~]20,000 years, coincidently after the divergence of Europeans and East Asians. TSPAN10 (rs9747347) is significantly associated with both myopia and pigmentation in Europeans, and we found selection favored the myopia risk allele in EUR. Haplotype comparison highlighted the divergence between EAS and EUR in RHO and pigmentation-associated loci, and the frequency diversity in Admixed American (AMR) of these loci was found to originate from recent admixture and local adaptation. We concluded that local adaptation played a role in myopia prevalence deviation, and selective pressure in the myopia-associated loci may originate from adaptation to sunlight environments rather than myopia itself. These findings reveal traces of evolution history of myopias genetic background, providing a new aspect of understanding the patterns and diversity of myopia prevalence. Author SummaryThe explanation for the distinct bias of myopia prevalence among ethnicities remains controversial, we took an evolutionary approach to understanding the history and diversity of the genetic background of myopia. We detected selection signatures of myopia-associated loci near the rhodopsin gene (RHO) in the 1000 Genome Project Europeans. Ambient light exposure is crucial for myopia; RHO is mainly expressed in rod cells and is extremely sensitive to light, indicating that local adaptation might contribute to myopia prevalence bias. Parallel geographical disposition of allele frequencies of myopia-associated loci in RHO and pigmentation-associated markers was observed, implying that selective pressure in myopia-associated loci may originate from adaptation events involved in sunlight exposure rather than myopia itself.