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MS thesis Cheng Cao.pdf (527.86 KB)

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Analysis of Concordance and Discordance in Genetic Association Studies via Forward-Backward Scoring Scheme

Cao, Cheng
http://rave.ohiolink.edu/etdc/view?acc_num=osu1595377667847233

Abstract Details

2020, Master of Science, Ohio State University, Statistics.
Consistency and inconsistency have been crucial features for effects of genetic variants in multiple genome-wide association studies (GWAS). Consistent significance across multiple independent studies is a powerful evidence in favor of disease-causing associations, which is the main purpose of replication/validation study and related approaches quantifying replicability. However, the analysis of replicability ignores the information of consistent insignificance and inconsistency, both of which contribute to the depiction of genetic architecture. To assess thorough characteristics of genetic variants across multiple studies, we proposed a concordance and discordance study to identify locus-specific consistency and inconsistency based on the magnitude of the genetic effects. In the context of two independent GWAS, the analysis classifies markers into concordant significance and insignificance, or two types of discordant significance. The former groups reinforces the credibility of inference, while the latter may provide insight into knowledge of underlying biological difference. In the light of two-stage procedures (2sfdr or r-value) measuring replicability, we established a Forward-Backward Scoring scheme (FBS) and named them FBS-2sfdr or FBS-rv, respectively, to allocate genetic variants into concordant sets or discordant sets. We further adapted two other methods, an obvious extension of a single GWAS, termed naive approach, and Cartesian hidden Markov model (CHMM) for the analysis of concordance and discordance. We then carried out simulation studies and compared performance of the four before-mentioned approaches. Due to the limitation of CHMM on dependent follow-up study and low efficiency of the naive approach according to simulation results, we applied FBS-2sfdr and FBS-rv on previous GWAS of well-known complex diseases Crohn's disease (CD) and type 2 diabetes (T2D) using symmetric and asymmetric study designs. Compared with replicability and reproducibility, concordance/discordance may be more accurate terminology to describe the simultaneous performance of a genetic variant across multiple studies. Moreover, the analysis of concordance and discordance and the proposed methods leads to greater biological insights. The classification not only improves the delineation of systematic genome-wide patterns, but potentially gives interpretation of biological-driven heterogeneity between two independent studies.
Lin Shili (Advisor)
Chang Lo-bin (Committee Member)
96 p.
Statistics

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Citations

  • Cao, C. (2020). Analysis of Concordance and Discordance in Genetic Association Studies via Forward-Backward Scoring Scheme [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1595377667847233

    APA Style (7th edition)

  • Cao, Cheng. Analysis of Concordance and Discordance in Genetic Association Studies via Forward-Backward Scoring Scheme. 2020. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1595377667847233.

    MLA Style (8th edition)

  • Cao, Cheng. "Analysis of Concordance and Discordance in Genetic Association Studies via Forward-Backward Scoring Scheme." Master's thesis, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1595377667847233

    Chicago Manual of Style (17th edition)

osu1595377667847233
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