title: A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study.
abstract: Age-related maculopathy (ARM) is a leading cause of visual impairment among the elderly in Western populations. To identify ARM-susceptibility loci, we genotyped a subset of subjects from the Beaver Dam (WI) Eye Study and performed a model-free genomewide linkage analysis for markers linked to a quantitative measure of ARM. We initially genotyped 345 autosomal markers in 325 individuals (N=263 sib pairs) from 102 pedigrees. Ten regions suggestive of linkage with ARM were observed on chromosomes 3, 5, 6, 12, 15, and 16. Prior to fine mapping, the most significant regions were an 18-cM region on chromosome 12, near D12S1300 (P=.0159); a region on chromosome 3, near D3S1763, with a P value of.0062; and a 6-cM region on chromosome 16, near D16S769, with a P value of.0086. After expanding our analysis to include 25 additional fine-mapping markers, we found that a 14-cM region on chromosome 12, near D12S346 (located at 106.89 cM), showed the strongest indication of linkage, with a P value of.004. Three other regions, on chromosomes 5, 6, and 15, that were nominally significant at P< or =.01 are also appropriate for fine mapping.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44109-1998, USA. texilene@darwin.EPBI.cwru.edu
authors.forename: James H
authors.initials: JH
authors.lastname: Schick
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Klein
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Karlie
authors.initials: K
authors.lastname: Reading
authors.forename: Rachel
authors.initials: R
authors.lastname: Liptak
authors.forename: Christopher
authors.initials: C
authors.lastname: Millard
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Tomany
authors.forename: Emily L
authors.initials: EL
authors.lastname: Moore
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Fijal
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D002885:Chromosomes, Human, Pair 16; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D035781:Siblings; D014922:Wisconsin
chemical_list: D005819:Genetic Markers