In summary, while quite successful for traits showing mendelian inheritance patterns, linkage analysis had not proven very tractable for most multifactorial diseases, and many ocular disorders and traits lag in gene identification. The difficulties in mapping these disease genes have been owing to genetic heterogeneity (different loci segregating in different samples), modest sample sizes that have not been sufficiently large to extract the linkage signal (ie, small effect size of the disease gene), phenotypic heterogeneity, and epistasis (interaction between genes). Thus, gene discovery for most ocular traits is still in the early phase, the exception being AMD, which has had successful breakthroughs in disease gene mapping despite its complexity. Two loci, complement factor H and LOC387715, were identified as major candidate genes underneath linkage peaks on chromosomes 1q50- 52 and 10q,53,54 following linkage experiments. More convincingly, the majority of the studies published have shown some support for both loci. Further, the linkage scans for AMD have been surprisingly concordant in identification of multiple regions likely to harbor a candidate gene beyond the loci on chromosomes 1 and 10, which showed the best evidence for linkage in a meta-analysis for AMD.55 Similarly, there seems to be a convergence of evidence on chromosomes 5q and 14q for glaucoma susceptibility,15,56 although a disease locus has not yet been identified. Therefore, the prospects of using family-based methods to map disease genes for ocular diseases are quite favorable.