title: Digital quantification of human eye color highlights genetic association of three new loci.
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.
authors.affiliation: Department of Forensic Molecular Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollstein
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Ankra-Badu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.forename: Gu
authors.initials: G
authors.lastname: Zhu
authors.forename: Mats
authors.initials: M
authors.lastname: Larsson
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Susan
authors.initials: S
authors.lastname: Walsh
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005127:Eye Color; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010781:Photography; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D055815:Young Adult
references.citation: Am J Phys Anthropol. 1975 Nov;43(3):387-91
references.pmid: 1211433
references.citation: Am J Phys Anthropol. 2007;Suppl 45:85-105
references.pmid: 18046745
references.citation: Am J Hum Genet. 2008 Feb;82(2):411-23
references.pmid: 18252221
references.citation: Mol Hum Reprod. 2006 Nov;12(11):671-6
references.pmid: 16973828
references.citation: Am Fam Physician. 1999 Jan 15;59(2):381-90, 392, 395-6
references.pmid: 9930130
references.citation: Eur J Epidemiol. 2007;22(11):819-29
references.pmid: 17955331
references.citation: Forensic Sci Int Genet. 2011 Jun;5(3):170-80
references.pmid: 20457092
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1205-14
references.pmid: 19029039
references.citation: Hum Genet. 2008 Mar;123(2):177-87
references.pmid: 18172690
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: DNA Res. 2002 Jun 30;9(3):89-97
references.pmid: 12168953
references.citation: Nature. 2008 Nov 6;456(7218):18-21
references.pmid: 18987709
references.citation: Eur J Hum Genet. 2007 Jan;15(1):94-102
references.pmid: 17063143
references.citation: Hum Genet. 2009 Jul;126(1):195-214
references.pmid: 19526251
references.citation: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):801-13
references.pmid: 18775863
references.citation: Nat Genet. 2008 Jul;40(7):835-7
references.pmid: 18488028
references.citation: Hum Mol Genet. 2009 Sep 15;18(18):3516-24
references.pmid: 19570815
references.citation: Curr Biol. 2009 Mar 10;19(5):R192-3
references.pmid: 19278628
references.citation: Am J Hum Genet. 2007 Feb;80(2):241-52
references.pmid: 17236130
references.citation: Am J Phys Anthropol. 2007 May;133(1):779-80; author reply 780-1
references.pmid: 17326100
references.citation: Hum Genet. 2005 Apr;116(5):402-6
references.pmid: 15726415
references.citation: Eye (Lond). 2002 Nov;16(6):710-4
references.pmid: 12439664
references.citation: Am J Hum Genet. 2008 Feb;82(2):424-31
references.pmid: 18252222
references.citation: Eur J Epidemiol. 2009;24(9):553-72
references.pmid: 19728115
references.citation: Nat Genet. 2007 Dec;39(12):1443-52
references.pmid: 17952075
references.citation: Annu Rev Genomics Hum Genet. 2009;10:387-406
references.pmid: 19715440
references.citation: Twin Res. 2003 Jun;6(3):192-200
references.pmid: 12855068
references.citation: Eur J Epidemiol. 1991 Jul;7(4):403-22
references.pmid: 1833235
references.citation: Mol Biol Evol. 2006 Sep;23(9):1697-706
references.pmid: 16757656
references.citation: BMC Genet. 2007 Aug 16;8:56
references.pmid: 17705851
references.citation: Pigment Cell Melanoma Res. 2009 Oct;22(5):544-62
references.pmid: 19619260
references.citation: Pharmacogenomics. 2008 Jun;9(6):703-15
references.pmid: 18518849
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Bioinformatics. 2007 May 15;23(10):1294-6
references.pmid: 17384015
references.citation: Nat Genet. 2009 Apr;41(4):399-406
references.pmid: 19305408
references.citation: Eur J Clin Pharmacol. 2006 Oct;62(10):829-37
references.pmid: 16909274
references.citation: Forensic Sci Int Genet. 2009 Jun;3(3):154-61
references.pmid: 19414162
references.citation: J Med Genet. 2009 Sep;46(9):614-6
references.pmid: 19508968
references.citation: Curr Opin Hematol. 2008 Jan;15(1):22-9
references.pmid: 18043242
references.citation: PLoS Genet. 2008 May 16;4(5):e1000074
references.pmid: 18483556