title: Testing optimally weighted combination of variants for hypertension.
abstract: Testing rare variants directly is possible with next-generation sequencing technology. In this article, we propose a sliding-window-based optimal-weighted approach to test for the effects of both rare and common variants across the whole genome. We measured the genetic association between a disease and a combination of variants of a single-nucleotide polymorphism window using the newly developed tests TOW and VW-TOW and performed a sliding-window technique to detect disease-susceptible windows. By applying the new approach to unrelated individuals of Genetic Analysis Workshop 18 on replicate 1 chromosome 3, we detected 3 highly susceptible windows across chromosome 3 for diastolic blood pressure and identified 10 of 48,176 windows as the most promising for both diastolic and systolic blood pressure. Seven of 9 top variants influencing diastolic blood pressure and 8 of 9 top variants influencing systolic blood pressure were found in or close to our top 10 windows.
authors.affiliation: Joseph J.Zilber School of Public Health,University of Wisconsin, P.O. Box 413, Milwaukee, WI 53201, USA.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Mathematical Sciences, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Sha
authors.affiliation: Department of Mathematical Sciences, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Joseph J.Zilber School of Public Health,University of Wisconsin, P.O. Box 413, Milwaukee, WI 53201, USA.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Wang