title: Identification of rare variants for hypertension with incorporation of linkage information.
abstract: We conducted linkage analysis using the genome-wide association study data on chromosome 3, and then assessed association between hypertension and rare variants of genes located in the regions showing evidence of linkage. The rare variants were collapsed if their minor allele frequencies were less than or equal to the thresholds: 0.01, 0.03, or 0.05. In the collapsing process, they were either unweighted or weighted by the nonparametric linkage log of odds scores in 2 different schemes: exponential weighting and cumulative weighting. Logistic regression models using the generalized estimating equations approach were used to assess association between the collapsed rare variants and hypertension adjusting for age and gender. Evidence of association from the weighted and unweighted collapsing schemes with minor allele frequencies ≤0.01, after accounting for multiple testing, was found for genes DOCK3 (p = 0.0090), ARMC8 (p = 1.29E-5), KCNAB1 (p = 5.8E-4), and MYRIP (p = 5.79E-6). DOCK3 and MYRIP are newly discovered. Incorporating linkage scores as weights was found to help identify rare causal variants with a large effect size.
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli 35053, Taiwan, ROC.
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli 35053, Taiwan, ROC.
authors.forename: Ren-Hua
authors.initials: RH
authors.lastname: Chung
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli 35053, Taiwan, ROC.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli 35053, Taiwan, ROC.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Kao
authors.affiliation: Department of Biostatistics, Yale School of Public Health, 60 College Street, New Haven, Connecticut 06520, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, 1834 Wake Forest Rd., Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu