title: Considering interactive effects in the identification of influential regions with extremely rare variants via fixed bin approach.
abstract: In this study, we analyze the Genetic Analysis Workshop 18 (GAW18) data to identify regions of single-nucleotide polymorphisms (SNPs), which significantly influence hypertension status among individuals. We have studied the marginal impact of these regions on disease status in the past, but we extend the method to deal with environmental factors present in data collected over several exam periods. We consider the respective interactions between such traits as smoking status and age with the genetic information and hope to augment those genetic regions deemed influential marginally with those that contribute via an interactive effect. In particular, we focus only on rare variants and apply a procedure to combine signal among rare variants in a number of "fixed bins" along the chromosome. We extend the procedure in Agne et al [1] to incorporate environmental factors by dichotomizing subjects via traits such as smoking status and age, running the marginal procedure among each respective category (i.e., smokers or nonsmokers), and then combining their scores into a score for interaction. To avoid overlap of subjects, we examine each exam period individually. Out of a possible 629 fixed-bin regions in chromosome 3, we observe that 11 show up in multiple exam periods for gene-smoking score. Fifteen regions exhibit significance for multiple exam periods for gene-age score, with 4 regions deemed significant for all 3 exam periods. The procedure pinpoints SNPs in 8 "answer" genes, with 5 of these showing up as significant in multiple testing schemes (Gene-Smoking, Gene-Age for Exams 1, 2, and 3).
authors.affiliation: Department of Statistics, Columbia University, 1255 Amsterdam Avenue, Room 1005, MC 4690, New York, New York 10027, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Agne
authors.affiliation: Department of Statistics, Columbia University, 1255 Amsterdam Avenue, Room 1005, MC 4690, New York, New York 10027, USA.
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Information Systems, Business Statistics and Operations Management, Hong Kong University of Science and Technology Business School, Hong Kong.
authors.forename: Inchi
authors.initials: I
authors.lastname: Hu
authors.affiliation: Division of Biostatistics, School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong.
authors.forename: Haitian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Statistics, Columbia University, 1255 Amsterdam Avenue, Room 1005, MC 4690, New York, New York 10027, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Statistics, Columbia University, 1255 Amsterdam Avenue, Room 1005, MC 4690, New York, New York 10027, USA.
authors.forename: Shaw-Hwa
authors.initials: SH
authors.lastname: Lo