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Anthony Musolf, Claire L. Simpson, Laura Portas, Federico Murgia, Qing Li, Elise Ciner, Dwight Stambolian, Joan E Bailey-Wilson; Myopia is Significantly Linked to Chromosomes 7p14.3 and 17p13.2 Across Five Discrete Populations. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3146.
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Myopia is one of the most common eye diseases in the world, affecting nearly one quarter of all Americans. It is a complex disease with risk increased by both environmental and genetic factors, however the genetic factors are still not well elucidated. Our study uses families from multiple ethnic groups with a family history of myopia to try to identify genetic linkage between particular genetic variants and myopia risk.
We analyzed over 1000 patients with exome enriched array genotypes from over 250 extended pedigrees. The data contained five discrete populations: African-Americans, Han Chinese, European-Americans (Caucasians), and two specialized subgroups of Caucasians: Ashkenazi Jews and Pennsylvania Amish. The phenotype was myopia affection; individuals were coded as either affected, unaffected, or unknown. An autosomal dominant model with a disease allele frequency of 1% and a penetrance of 90% for carriers and 10% for non-carriers was used. Two-point linkage analysis was performed on each of the five populations individually. LOD scores were then combined across all populations and HLOD scores were calculated for the entire data set.
After combining across all five populations, we identified two genome-wide significant variants. The highest was rs2011974 (HLOD = 6.60), an intronic SNP located in AVL9 at 7p14.3. The other significant variant was rs55910638 (HLOD = 4.58), a nonsynonymous exonic SNP located in LOC728392 at 17p13.2. While neither gene has been previously implicated in myopia (and the function of LOC728392 is still unknown) both genes are expressed in the retina. A further 101 suggestive signals were also identified, with particularly large haplotypes at 4q22.1-23 (13 variants), 6q25.2-27 (8 variants), 8q23.1 (8 variants), and 13q34 (5 variants).
We have identified two significantly linked variants across five populations for myopia. The variants are located at 7p14.3 and 17p13.2. As it is possible that these variants are simply in linkage disequilibrium with the causal variants, we plan further targeted sequencing on the 7p and 17p regions to elucidate the causal variant(s).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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