Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q

Objective: To localize genes influencing ocular refraction in subjects in the Beaver Dam Eye Study. Previous studies establish that myopia clusters within families and linkage to myopia has been demonstrated on 2q, 4q, 12q, 17q, 18q, 22q, and Xq. Few studies have examined genetic effects across the entire range of refraction, though linkages to 1p, 3q, 4q, 8p, and 11p have been reported, and our previous analysis of the Beaver Dam Eye Study demonstrated substantial heritability for refraction (68%). Methods: We conducted nonparametric sibling-pair and genome-wide linkage analyses on spherical equivalent adjusting for age, education, and nuclear sclerosis, in 834 sibling pairs in 486 extended pedigrees. Results: We identified a novel region of suggestive linkage on 1q (multipoint, P < .00019) and replicated the 22q region (multipoint, P = .0033) previously linked to myopia. Additionally, there was some evidence of linkage to 7p (multipoint, P = .0023). Conclusion: Refraction is a complex trait influenced by both genes and environment. Our work confirms a previously reported linkage region on 22q and identifies 2 novel regions of linkage on 1q and 7p. Clinical Relevance: Further, genetic research is needed to finemap this trait to identify the causative gene. Modifying the actions of such a gene might lead to a reduction in the risk of refractive error.