The study focused attention on an Asian population in order to reduce heterogeneity of the genetic background. In 1995, a genetic network was established in the San Francisco Bay Area, Hawaii, and Taiwan, recruiting an estimated 1,700 affected hypertensive sibpairs plus several multigenerational hypertensive pedigrees of Asian Pacific Chinese and Japanese. Linkage analysis was used to map and identify the genes for hypertension in this ethnic group. A new genetic map of the human genome with 2041 ordered polymorphic markers with an average interval of less than 3 cM had been reported. Such a dense map of polymorphic markers made it plausible to propose linkage analysis of complex traits. A total genomic search was performed on 1700 affected sibpairs and family members. In addition, the candidate gene approach was also used. To address the possibility of heterogeneity of the hypertensive trait, a number of intermediate phenotypes was studied that may help identify more homogeneous subgroups of hypertension. For example, Asians and Pacific Islanders had an increased risk for hypertension, dyslipidemia, and glucose intolerance (Syndrome X) that were associated with hyperinsulinemia. Therefore, hypertension was investigated according to insulin sensitivity vs. resistance as well as other intermediate phenotypes related to hypertension pathophysiology such as renin, Ang II, and endothelin. The hypothesis was that by focusing on possible hypertensive subsets with well defined phenotypes, the possibility was enhanced of gene identification for hypertension in these patients. The third approach examined the hypothesis that there existed a dominant locus determining hypertension in a subset of affected individuals using the analysis of multigenerational pedigrees with 10-13 meiosis separating affected members. If such a subset existed, this approach would reduce the likelihood of heterogeneity and increase the probability of revealing genetic linkage. Once major gene loci were identified, it was important to determine the prevalence of these loci in the overall population and the risk associated with their loci for the development of hypertension. Therefore, the genetic epidemiology of the loci were studied using epidemiological methodologies such as association studies and case control analysis on well characterized populations in Hawaii and Taiwan that had been studied prospectively for many years.