Identification of rare variants for hypertension with incorporation of linkage information

BMC Proceedings

Proceedings

Fang-Chi Hsu¹  Lin Hou²  Chun-Yi Lee³  Hui-Yi Kao³  Yen-Feng Chiu³  Ren-Hua Chung³ 

[1] Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, 1834 Wake Forest Rd., 27157, Winston-Salem, NC, USA;Department of Biostatistics, Yale School of Public Health, 60 College Street, 06520, New Haven, Connecticut, USA;Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd., 35053, Zhunan, Miaoli, Taiwan, ROC;

关键词: False Discovery Rate;    Minor Allele Frequency;    Rare Variant;    Large Effect Size;    GWAS Data;   

DOI  :  10.1186/1753-6561-8-S1-S109

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Chiu et al.; licensee BioMed Central Ltd. 2014