Author Date

2019-07-24

Degree Name

Department

Public Health

College

Life Sciences

Defense Date

2019-07-23

Publication Date

2019-08-05

First Faculty Advisor

Dr. John Kauwe

First Faculty Reader

Dr. Evan Thacker

Honors Coordinator

Dr. Len Novilla

Keywords

Alzheimer's Disease, Epistasis, Genetics

Abstract

Alzheimer’s disease is the most common form of dementia among people age 65 and older. Because of the complexity of this disease, many studies have taken the epistatic approach to discover underlying genetic disorders. Epistasis is the study of gene-gene interaction in which the effects of one gene mask the effects of the other gene. In this study, we attempted to replicate two earlier studies that identified three gene-gene interactions. We used the 2019 Alzheimer’s Diseases Genetics Consortium (ADGC) dataset and we conducted a logistic regression with and without the interaction terms. The interactions we considered were between CLU rs11136000 and MS4A4E rs670139 (p-value = 0.537, OR = 0.97, 95% CI = 0.88,1.07), WWC1 rs3733980 and TLN2 rs7175766 in males (p-value = 0.745, OR = 0.98, 95% CI = 0.83, 1.14), and WWC1 rs1477307 and TLN2 rs4077746 in males (p-value = 0.996, OR = 0. 999, 95% CI = 0.85, 1.17). Analyses in this dataset failed to replicate any of the interactions, suggesting that iv previously-reported associations may be the result of more complex epistatic interactions, genetic heterogeneity, or false-positive associations due to limited sample sizes.