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Digital quantification of human eye color highlights genetic association of three new loci.

Liu F, Wollstein A, Hysi PG, Ankra-Badu GA, Spector TD, Park D, Zhu G, Larsson M, Duffy DL, Montgomery GW, Mackey DA, Walsh S, Lao O, Hofman A, Rivadeneira F, Vingerling JR, Uitterlinden AG, Martin NG, Hammond CJ, Kayser M - PLoS Genet. (2010)

Bottom Line: Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information.Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association.A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Molecular Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.

ABSTRACT
Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The LYST gene at 1q42.3 and the DSCR9 gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.

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Chromosome 21q22.13 locus associated with quantitative eye color in the Rotterdam Study (RS123).The chromosome 21 37.30–37.65 Mb region includes DSCR6, PIGP, TTC3, DSCR9, and DSCR3 genes, SNPs rs1003719, rs2252893, rs2835621, rs2835630, and rs7277820 showed genome-wide significant association with CHS1.
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pgen-1000934-g006: Chromosome 21q22.13 locus associated with quantitative eye color in the Rotterdam Study (RS123).The chromosome 21 37.30–37.65 Mb region includes DSCR6, PIGP, TTC3, DSCR9, and DSCR3 genes, SNPs rs1003719, rs2252893, rs2835621, rs2835630, and rs7277820 showed genome-wide significant association with CHS1.

Mentions: At the 1q42.3 locus two SNPs, rs3768056 and rs9782955, were associated with S at the genome-wide significance level (5.5×10−9<P<7.8×10−9) (Table 2, Figure 4). Both SNPs are located in introns of the lysosomal trafficking regulator (LYST) gene. Note that SNPs at this locus were associated with S but not with H or categorical colors, which is a different phenomenon compared to the other two new loci identified. Three SNPs at 17q25.3 were associated with multiple color traits at the genome-wide significance level and the association with CHS1 was the most significant (5.9×10−11<P<7.2×10−9) (Table 2, Figure 5). The SNP rs7219915 is intronic and rs9894429 exonic of the nuclear protein localization 4 homolog (NPLOC4) gene and rs12452184 is intronic of the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) gene. There are multiple small genes in the 17q25.3 region (Figure 5). Five SNPs at 21q22.13 were significantly associated with CHS1 (5.0×10−9<P<3.1×10−8) (Table 2, Figure 6). Four SNPs, rs1003719, rs2252893, rs2835621, and rs2835630, are intronic of the tetratricopeptide repeat domain 3 (TTC3) gene, and one, rs7277820, is in the flanking 5′ UTR region of the Down Syndrome Critical Region 9 (DSCR9) gene. The TTC3 and DSCR9 genes are in the same LD block (Figure 6).


Digital quantification of human eye color highlights genetic association of three new loci.

Liu F, Wollstein A, Hysi PG, Ankra-Badu GA, Spector TD, Park D, Zhu G, Larsson M, Duffy DL, Montgomery GW, Mackey DA, Walsh S, Lao O, Hofman A, Rivadeneira F, Vingerling JR, Uitterlinden AG, Martin NG, Hammond CJ, Kayser M - PLoS Genet. (2010)

Chromosome 21q22.13 locus associated with quantitative eye color in the Rotterdam Study (RS123).The chromosome 21 37.30–37.65 Mb region includes DSCR6, PIGP, TTC3, DSCR9, and DSCR3 genes, SNPs rs1003719, rs2252893, rs2835621, rs2835630, and rs7277820 showed genome-wide significant association with CHS1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865509&req=5

pgen-1000934-g006: Chromosome 21q22.13 locus associated with quantitative eye color in the Rotterdam Study (RS123).The chromosome 21 37.30–37.65 Mb region includes DSCR6, PIGP, TTC3, DSCR9, and DSCR3 genes, SNPs rs1003719, rs2252893, rs2835621, rs2835630, and rs7277820 showed genome-wide significant association with CHS1.
Mentions: At the 1q42.3 locus two SNPs, rs3768056 and rs9782955, were associated with S at the genome-wide significance level (5.5×10−9<P<7.8×10−9) (Table 2, Figure 4). Both SNPs are located in introns of the lysosomal trafficking regulator (LYST) gene. Note that SNPs at this locus were associated with S but not with H or categorical colors, which is a different phenomenon compared to the other two new loci identified. Three SNPs at 17q25.3 were associated with multiple color traits at the genome-wide significance level and the association with CHS1 was the most significant (5.9×10−11<P<7.2×10−9) (Table 2, Figure 5). The SNP rs7219915 is intronic and rs9894429 exonic of the nuclear protein localization 4 homolog (NPLOC4) gene and rs12452184 is intronic of the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) gene. There are multiple small genes in the 17q25.3 region (Figure 5). Five SNPs at 21q22.13 were significantly associated with CHS1 (5.0×10−9<P<3.1×10−8) (Table 2, Figure 6). Four SNPs, rs1003719, rs2252893, rs2835621, and rs2835630, are intronic of the tetratricopeptide repeat domain 3 (TTC3) gene, and one, rs7277820, is in the flanking 5′ UTR region of the Down Syndrome Critical Region 9 (DSCR9) gene. The TTC3 and DSCR9 genes are in the same LD block (Figure 6).

Bottom Line: Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information.Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association.A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study.

View Article: PubMed Central - PubMed

Affiliation: Department of Forensic Molecular Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.

ABSTRACT
Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The LYST gene at 1q42.3 and the DSCR9 gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.

Show MeSH
Related in: MedlinePlus