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) andNTN1(FDR-p: 4.98*10–8), stood out as promising candidates.PIWIL4is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis whileMBD2andNTN1are 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), andMC5R(FDR-p: 2.10*10–8), were considered promising candidates.VPS54is reported to be associated with Retinitis pigmentosa;IQGAP1is reported to regulate choroidal vascularization in Age-Related Macular Degeneration;NMBis involved in RPE homeostasis regulation;MC5Ris 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.