Taiwan schizophrenia linkage study: Lessons learned from endophenotype‐based genome‐wide linkage scans and perspective

AbstractTaiwan Schizophrenia Linkage Study (TSLS) was initiated with a linkage strategy for locating multiple genes, each of small to moderate effect, and aimed to recruit a large enough sample of pairs of affected siblings and their families ascertained from a multisite study. With a sample of 607 families successfully recruited, a total of 2,242 individuals (1,207 affected and 1,035 unaffected) from 557 families were genotyped using 386 microsatellite markers spaced at an average of 9‐cM intervals. Here the author reviews the establishment of TSLS and initial signal derived from linkage scan using the diagnosis of schizophrenia. Based on the limited success of the initial linkage analysis, a sufficient‐component causal model is proposed to incorporate endophenotypes and genes for schizophrenia. Four types of candidate endophenotype measured in TSLS, including schizotypal personality, Continuous Performance Test, Wisconsin Card Sorting Test, and niacin skin flush test, are briefly described. The author discusses different strategies of linkage analysis incorporating these endophenotypes, including quantitative trait loci (QTL) linkage analysis, clustering‐derived subgroups, ordere