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Multi-trait Analysis of Genome-wide Association Studies using Adaptive Fisher's Method

Deng, Qiaolan
http://orcid.org/0000-0002-7591-4355
http://rave.ohiolink.edu/etdc/view?acc_num=osu1650543249848112

Abstract Details

2022, Doctor of Philosophy, Ohio State University, Biostatistics.
Genome-wide association studies (GWAS) have identified a large number of genetic variants associated with human traits or diseases. Despite these successes, much of the heritability of many traits is still unaccounted for. Commonly used single-trait analysis methods in GWAS are conservative, while multi-trait methods improve statistical power by integrating association evidence across multiple traits. My dissertation research focuses on developing multi-trait methods for GWAS and I have developed two multi-trait methods. The first one, multi-trait adaptive Fisher's method (MTAF), is a multi-trait method using individual-level genotype data. It combines p-values adaptively and showed robust power performance in simulation studies. We applied MTAF to a dataset --- Study of Addiction: Genetics and Environment (SAGE) and identified genes associated with substance addiction. In contrast to individual-level genotype, GWAS summary statistics are usually more readily available publicly, and thus methods using only summary statistics have greater usage. Therefore, in the second part of the thesis, we developed MTAFS, an adaptive and robust method for multi-trait analysis of GWAS using summary statistics. In addition to its robust performance, its computational efficiency is greatly improved compared with MTAF by avoiding permutations. MTAFS was applied to a brain imaging dataset from the UK biobank and identified genes associated with brain functions.
Shili Lin (Advisor)
Chi Song (Advisor)
Kellie Archer (Committee Member)
Ai Ni (Committee Member)
154 p.
Biostatistics; Genetics; Statistics
GWAS; SNP; statistical genetics; summary statistics; adaptive method; adaptive Fisher's method; deep phenotyping data

Recommended Citations

Citations

  • Deng, Q. (2022). Multi-trait Analysis of Genome-wide Association Studies using Adaptive Fisher's Method [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1650543249848112

    APA Style (7th edition)

  • Deng, Qiaolan. Multi-trait Analysis of Genome-wide Association Studies using Adaptive Fisher's Method. 2022. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1650543249848112.

    MLA Style (8th edition)

  • Deng, Qiaolan. "Multi-trait Analysis of Genome-wide Association Studies using Adaptive Fisher's Method." Doctoral dissertation, Ohio State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=osu1650543249848112

    Chicago Manual of Style (17th edition)

osu1650543249848112
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This open access ETD is published by The Ohio State University and OhioLINK.