Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study.
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2005-12-30
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Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.
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Li, YJ, ER Martin, L Zhang and AS Allen (2005). Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study. BMC Genet, 6 Suppl 1. p. S53. 10.1186/1471-2156-6-S1-S53 Retrieved from https://hdl.handle.net/10161/10631.
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Scholars@Duke
Yi-Ju Li
My research interest is in statistical genetics, including statistical method development and its application for understanding the genetic predisposition of human complex diseases. Here is the list of research topics:
- Statistical genetics: development of family-based association methods for quantitative traits with or without censoring and for detecting X-linked genes for disease risk. With the availability of next generation sequencing data, we have ongoing projects to develop the association methods for testing rare variants for different phenotypic measures.
- Genetics of Alzheimer's disease (AD) and Fuchs endothelial corneal dystrophy (FECD).
- Genetic basis of age-at-onset of Alzheimer disease.
- Peri-operative genomic studies. Investigate the genetic risk factors for postoperative outcomes of patients underwent non-emergent coronary artery bypass grafting with cardiopulmonary bypass.
Andrew Scott Allen
My research focuses on developing new statistical methods for identifying susceptibility loci involved in complex human disease. It involves a mix of genetics, statistics, and computer science and is motivated by the complexities of real data encountered in collaborative disease-gene mapping projects.
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