TY - JOUR
T1 - A Genome Scan for Eye Color in 502 Twin Families
T2 - Most Variation is due to a QTL on Chromosome 15q
AU - Zhu, Gu
AU - Evans, David M.
AU - Duffy, David L.
AU - Montgomery, Grant W.
AU - Medland, Sarah E.
AU - Gillespie, Nathan A.
AU - Ewen, Kelly R.
AU - Jewell, Mary
AU - Liew, Yew Wah
AU - Hayward, Nicholas K.
AU - Sturm, Richard A.
AU - Trent, Jeffrey M.
AU - Martin, Nicholas G.
N1 - Funding Information:
Collection of phenotypes and DNA samples was supported by grants from the Queensland Cancer Fund (NGM, NKH), the Australian National Health and Medical Research Council (950998, 981339 and 241944; NGM), and the US National Cancer Institute (CA88363; NKH, NGM, DLD, RAS, GWM). The genome scans were supported by the Australian NHMRC’s Program in Medical Genomics (NHMRC-219178; NGM, GWM, DLD) and the Center for Inherited Disease Research (CIDR; Director, Dr Jerry Roberts) at The Johns Hopkins University (JMT, NGM). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (Contract Number N01-HG-65403). We thank Dr Cathy Hyland of the Australian Red Cross Blood Service, Brisbane, for initiating blood grouping; the twins and the staff in the Red Cell Reference Laboratory; Ann Eldridge, Marlene Grace and Anjali Henders for assistance; and the twins, their siblings, and their parents for their cooperation. We thank Dorret Boomsma and Danielle Posthuma for incisive comments on the manuscript.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2004/4
Y1 - 2004/4
N2 - We have rated eye color on a 3-point scale (1 = blue/grey, 2 = hazel/green, 3 = brown) in 502 twin families and carried out a 5-10 cM genome scan (400-757 markers). We analyzed eye color as a threshold trait and performed multipoint sib pair linkage analysis using variance components analysis in Mx. A lod of 19.2 was found at the marker D15S1002, less than 1 cM from OCA2, which has been previously implicated in eye color variation. We estimate that 74% of variance in eye color liability is due to this QTL and a further 18% due to polygenic effects. However, a large shoulder on this peak suggests that other loci affecting eye color may be telomeric of OCA2 and inflating the QTL estimate. No other peaks reached genome-wide significance, although lods > 2 were seen on 5p and 14q and lods > 1 were additionally seen on chromosomes 2, 3, 6, 7, 8, 9, 17 and 18. Most of these secondary peaks were reduced or eliminated when we repeated the scan as a two locus analysis with the 15q linkage included, although this does not necessarily exclude them as false positives. We also estimated the interaction between the 15q QTL and the other marker locus but there was only minor evidence for additive x additive epistasis. Elaborating the analysis to the full two-locus model including non-additive main effects and interactions did not strengthen the evidence for epistasis. We conclude that most variation in eye color in Europeans is due to polymorphism in OCA2 but that there may be modifiers at several other loci.
AB - We have rated eye color on a 3-point scale (1 = blue/grey, 2 = hazel/green, 3 = brown) in 502 twin families and carried out a 5-10 cM genome scan (400-757 markers). We analyzed eye color as a threshold trait and performed multipoint sib pair linkage analysis using variance components analysis in Mx. A lod of 19.2 was found at the marker D15S1002, less than 1 cM from OCA2, which has been previously implicated in eye color variation. We estimate that 74% of variance in eye color liability is due to this QTL and a further 18% due to polygenic effects. However, a large shoulder on this peak suggests that other loci affecting eye color may be telomeric of OCA2 and inflating the QTL estimate. No other peaks reached genome-wide significance, although lods > 2 were seen on 5p and 14q and lods > 1 were additionally seen on chromosomes 2, 3, 6, 7, 8, 9, 17 and 18. Most of these secondary peaks were reduced or eliminated when we repeated the scan as a two locus analysis with the 15q linkage included, although this does not necessarily exclude them as false positives. We also estimated the interaction between the 15q QTL and the other marker locus but there was only minor evidence for additive x additive epistasis. Elaborating the analysis to the full two-locus model including non-additive main effects and interactions did not strengthen the evidence for epistasis. We conclude that most variation in eye color in Europeans is due to polymorphism in OCA2 but that there may be modifiers at several other loci.
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U2 - 10.1375/136905204323016186
DO - 10.1375/136905204323016186
M3 - Article
C2 - 15169604
AN - SCOPUS:11144355855
SN - 1369-0523
VL - 7
SP - 197
EP - 210
JO - Twin Research
JF - Twin Research
IS - 2
ER -