Myopia in African Americans Is Significantly Linked to Chromosome 7p15.2-14.2

Abstract

The purpose of this study was to perform genetic linkage analysis and association analysis on exome genotyping from highly aggregated African American families with nonpathogenic myopia. African Americans are a particularly understudied population with respect to myopia. METHODS.One hundred six African American families from the Philadelphia area with a family history of myopia were genotyped using an Illumina ExomePlus array and merged with previous microsatellite data. Myopia was initially measured in mean spherical equivalent (MSE) and converted to a binary phenotype where individuals were identified as affected, unaffected, or unknown. Parametric linkage analysis was performed on both individual variants (single-nucleotide polymorphisms [SNPs] and microsatellites) as well as gene-based markers. Family-based association analysis and transmission disequilibrium test (TDT) analysis modified for rare variants was also performed. RESULTS.Genetic linkage analysis identified 2 genomewide significant variants at 7p15.2 and 7p14.2 (in the intergenic region between MIR148A and NFE2L3 and in the noncoding RNA LOC401324) and 2 genomewide significant genes (CRHR2 and AVL9) both at 7p14.3. No genomewide results were found in the association analyses. CONCLUSIONS.This study identified a significant linkage peak in African American families for myopia at 7p15.2 to 7p14.2, the first potential risk locus for myopia in African Americans. Interesting candidate genes are located in the region, including PDE1C, which is highly expressed in the eyes, and known to be involved in retinal development. Further identification of the causal variants at this linkage peak will help elucidate the genetics of myopia in this understudied population.

Crosstalk between heredity and environment in myopia: An overview

“…Recently, Simpson, C. L. and colleagues identified a significant chain peak of myopia in African American families at 7p15.2 and 7p14.2 [ 30 ]; meanwhile, Musolf AM et al [ 31 ] also reported a significant genetic linkage peak of myopia in Chinese Han patients at 10q26. 13.…”

“… 2017 [ 26 ] TNFRSF21 Pan, H. 2019 [ 27 ] AGRN Zheng, Y. H. 2021 [ 28 ] P4HA2 Napolitano, F. 2018 [ 29 ] 7p15.2 and 7p14.2 Simpson, C.L. 2021 [ 30 ] 10q26. 13.…”

Unveiling Digenic Pathogenic Variants and Mutation Susceptibility in Chinese Patients with Suspected Retinitis Pigmentosa

“…The Transmission Disequilibrium Test (TDT) stands out as a powerful tool for pinpointing disease-associated loci that exhibit strong genetic in uence in complex disorders, often mirroring the behavior of Mendelian alleles in monogenic conditions within trio family cohorts [20,21]. Diverging from traditional case-focused sequencing strategies that prioritize exons and splice junctions to uncover mutations adhering to classic Mendelian patterns, TDT facilitates the unbiased discovery of disease-related loci throughout the genome, without heavy reliance on presupposed models of inheritance [22][23][24]. Consequently, TDT can enhance existing sequencing methodologies by uncovering signi cant genetic factors that may otherwise remain undetected…”

Toward Eliminating Visual Impairment Due to Refractive Error

“…Any comparison of the African American participants in this analysis with other minority or even nonminority groups needs to be considered within the context of both the genetic and the SDOH environment at the time the study was performed. Although African American individuals with myopia have been found to have a specific chromosomal linkage, 5 it remains unclear if this genetic association makes refractive errors more or less common than the refractive errors found in other racial and ethnic populations. 6,7 Similarly, although Dhablania et al 1 were able to capture many aspects of SDOH, it is very difficult to compare their results with other studies performed many years earlier when the SDOH environment was likely to be very different and not as thoroughly assessed.…”