Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations

Giuseppe Giovanni Nardone; Beatrice Spedicati; Maria Pina Concas; Aurora Santin; Anna Morgan; Lorenzo Mazzetto; Maurizio Battaglia-Parodi; Giorgia Girotto

doi:10.3389/fgene.2023.1161696

Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations

Front Genet. 2023 Jun 9:14:1161696. doi: 10.3389/fgene.2023.1161696. eCollection 2023.

Authors

Giuseppe Giovanni Nardone¹, Beatrice Spedicati^{1

2}, Maria Pina Concas², Aurora Santin¹, Anna Morgan², Lorenzo Mazzetto¹, Maurizio Battaglia-Parodi³, Giorgia Girotto^{1

2}

Affiliations

¹ Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
² Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
³ Ophthalmology Department, Vita-Salute San Raffaele University, Milano, Italy.

Abstract

Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms. Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed. Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10^-9), MBD2 (FDR-p: 4.97*10^-8) and NTN1 (FDR-p: 4.98*10^-8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10^-9), IQGAP (FDR-p: 6,52*10^-10), NMB (FDR-p: 8.34*10^-11), and MC5R (FDR-p: 2.10*10^-8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function. Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.

Keywords: Deutan; Protan; Silk Road; Tritan; color vision defects; genetic isolates; genome wide association study; pathway analysis.

Grants and funding

This research was supported by D70-RESRICGIROTTO to GG.