The aim of the study was to perform a genetic linkage analysis for eye color, for comparative data. Similarity in eye color of mono- and dizygotic twins was rated by the twins’ mother, their father and/or the twins themselves. For 4748 twin pairs the similarity in eye color was available on a three point scale (“not at all alike”—“somewhat alike”—“completely alike”), absolute eye color on individuals was not assessed. The probability that twins were alike for eye color was calculated as a weighted average of the different responses of all respondents on several different time points. The mean probability of being alike for eye color was 0.98 for MZ twins (2167 pairs), whereas the mean probability for DZ twins was 0.46 (2537 pairs), suggesting very high heritability for eye color. For 294 DZ twin pairs genome-wide marker data were available. The probability of being alike for eye color was regressed on the average amount of IBD sharing. We found a peak LOD-score of 2.9 at chromosome 15q, overlapping with the region recently implicated for absolute ratings of eye color in Australian twins [Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y. W., Hayward, N. K., Sturm, R. A., Trent, J. M., and Martin, N. G. (2004). Twin Res. 7:197–210] and containing the OCA2 gene, which is the major candidate gene for eye color [Sturm, R. A. Teasdale, R. D, and Box, N. F. (2001). Gene 277:49–62]. Our results demonstrate that comparative measures on relatives can be used in genetic linkage analysis.
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Acknowledgments
Financial support is provided by Grant 904-61-090 from the Netherlands Organization for Scientific Research (NWO) Spinoza, the National Supercomputing Facilities (NCF (NWO/NCF sg208/sg214/sg217) and the Human Frontiers of Science Program (Grant number rg0154/1998-B). DP is supported by GenomEUtwin Grant (EU/QLRT-2001-01254) and by NWO/MaGW VIDI 016-065-318. Collection of Australian phenotypes and DNA samples was supported by Grants from the Queensland Cancer Fund, the Australian National Health and Medical Research Council (950998, 981339 and 241944), and the U.S. National Cancer Institute (CA88363). The genome scans were supported by the Australian NHMRC’s Program in Medical Genomics [NHMRC-219178] and the Center for Inherited Disease Research (Director, Dr. Jerry Roberts) at Johns Hopkins University.
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Posthuma, D., Visscher, P.M., Willemsen, G. et al. Replicated Linkage for Eye Color on 15q Using Comparative Ratings of Sibling Pairs. Behav Genet 36, 12–17 (2006). https://doi.org/10.1007/s10519-005-9007-x
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DOI: https://doi.org/10.1007/s10519-005-9007-x