Age-related maculopathy: an expanded genome-wide can with evidence of uceptibility loci within the 1q31 and 17q25 region

PURPOE: We eek to identify genetic loci that contribute to age-related maculopathy uceptibility. METHOD: Familie coniting of at leat two ibling affected by age-related maculopathy were acertained uing eye care record and fundu photograph. Additional family member were ued to increae the power to detect linkage. Microatellite genotyping wa conducted by the National Heart, Lung and Blood Intitute Mammalian Genotyping ervice and the National Intitute of Health Center for Inherited Dieae Reearch. Linkage analye were conducted with parametric (autoomal dominant; heterogeneity lod core) and nonparametric method (all tatitic) uing three diagnotic model. Fale-poitive rate were determined from imulation uing actual pedigree and genotyping data. REULT: Under our leat tringent diagnotic model, model C, 860 affected individual from 391 familie (452 ib pair) were genotyped. ixty-five percent of the affected individual had evidence of exudative dieae. Four region, 1q31, 9p13, 10q26, and 17q25, howed multipoint heterogeneity lod core or all core of 2.0 or greater (under at leat one model). Under our mot tringent diagnotic model, model A, the 1q31 heterogeneity lod core wa 2.46 between D11660 and D11647. Under model C, the 17q25 heterogeneity lod core at D17928 wa 3.16. Uing a threhold of 1.5, additional loci on chromoome 2 and 12 were identified. CONCLUION: The locu on chromoome 1q31 independently confirm a report by Klein and aociate mapping an age-related maculopathy uceptibility gene to thi region. imulation indicate that the 1q31 and 17q25 loci are unlikely to be fale poitive. There wa no evidence that other known macular or retinal dytrophy candidate gene region are major contributor to the genetic of age-related maculopathy.