A Powerful Nonparametric Statistical Framework for Family-Based Association Analyses. Issue 1 (5th March 2015)

• Record Type: Journal Article
• Authors: Li, Ming; He, Zihuai; Schaid, Daniel J; Cleves, Mario A; Nick, Todd G; Lu, Qing
• Is Part Of: Genetics. Volume 200:Issue 1(2015)
• Page Start: 69
• Page End: 78
• Publication Date: 2015-03-05
• Subjects: population stratification -- pedigree structure -- within-family information -- between-family information -- nicotine dependence; Genetics -- Periodicals; 576.5
• DOI: 10.1534/genetics.115.175174
• Languages: English
• ISSNs: 0016-6731

Abstract

Abstract: Family-based study design is commonly used in genetic research. It has many ideal features, including being robust to population stratification (PS). With the advance of high-throughput technologies and ever-decreasing genotyping cost, it has become common for family studies to examine a large number of variants for their associations with disease phenotypes. The yield from the analysis of these family-based genetic data can be enhanced by adopting computationally efficient and powerful statistical methods. We propose a general framework of a family-based U -statistic, referred to as family- U, for family-based association studies. Unlike existing parametric-based methods, the proposed method makes no assumption of the underlying disease models and can be applied to various phenotypes ( e.g., binary and quantitative phenotypes) and pedigree structures ( e.g., nuclear families and extended pedigrees). By using only within-family information, it can offer robust protection against PS. In the absence of PS, it can also utilize additional information ( i.e., between-family information) for power improvement. Through simulations, we demonstrated that family- U attained higher power over a commonly used method, family-based association tests, under various disease scenarios. We further illustrated the new method with an application to large-scale family data from the Framingham Heart Study. By utilizing additional information ( i.e., between-family information), family- U confirmed a previous association of CHRNA 5 with nicotine dependence.