FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

TitleFARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.
Publication TypeJournal Article
Year of Publication2016
AuthorsChoi, S, Lee, S, Qiao, D, Hardin, M, Cho, MH, Silverman, EK, Park, T, Won, S
JournalGenet Epidemiol
Date Published2016 09

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods.

Alternate JournalGenet. Epidemiol.
PubMed ID27325607
PubMed Central IDPMC4981534
Grant ListR01 HL113264 / HL / NHLBI NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
R01 HL075478 / HL / NHLBI NIH HHS / United States
P01 HL105339 / HL / NHLBI NIH HHS / United States
K01 HL129039 / HL / NHLBI NIH HHS / United States
P01 HL114501 / HL / NHLBI NIH HHS / United States