Alzheimer's Disease Associated Genomic Variants Identified in White Populations are Present in African Americans at Risk for Alzheimer's Disease Due to Family History Public

Abstract

Importance: The underlying genetic variants that contribute to the neurodevelopment of familial Alzheimer’s Disease (AD) is poorly understood. Furthermore, most studies on the genetics of AD have been limited to White cohorts; therefore, exploring the prevalence of variants between White and African American populations can help determine if White derived SNPs are applicable to non-white cohorts. Further, comparing the prevalence of variants within cognitively normal White and African American individuals with familial history to those diagnosed with Alzheimer’s has the potential to identify “at-risk” genes.

 

Objective: To investigate the prevalence of known and recently identified single nucleotide polymorphisms (SNPs) among African American and White individuals either diagnosed with AD or at risk via parental history.

 

Design/Setting: Observational and longitudinal multi-center study.

 

Participants: 160 cognitively normal and 55 Alzheimer’s Disease diagnosed African American and White individuals with parental history of Alzheimer’s disease.

 

Main Outcome and Measure: Genotyped whole blood samples

 

Results: 97.8% of the SNPs screened should be viable for screening in African American cohorts. Further, we report no significant results between the at-risk and Alzheimer’s diagnosed cohorts, suggesting that the genetic markers of AD are complex and not one gene contributes to the neurodevelopment of AD. 

 

Conclusion and Relevance: Alzheimer’s-associated variants identified in White populations may be applicable to assess the development of familial Alzheimer’s Disease within other populations such as African Americans, but all variants must be validated at a per SNP level. Furthermore, our results emphasize the complexity of Alzheimer’s Disease and how its development and progression is dependent on genetic, environmental, and lifestyle factors.

Table of Contents

Table of Contents 

Introduction .................................................................................................................................1 

Methods .......................................................................................................................................5 

Study Sample: ...............................................................................................................................5 

Genotyping: ..................................................................................................................................6 

Data Analysis: ...............................................................................................................................6 

Results ..........................................................................................................................................9 

Participant Demographics ..............................................................................................................9 

SNP Summary ..............................................................................................................................10 

Race Association Analysis .............................................................................................................10 

Diagnosis Association Analysis ......................................................................................................11 

Discussion ....................................................................................................................................13 

References ....................................................................................................................................19 

Tables ..........................................................................................................................................30 

Table 1: Patient Demographics.......................................................................................................30 

Table 2: SNP Summary For All Screened Variants. ............................................................................31 

Table 3: Race Association Analysis Results ......................................................................................34 

Table 4: Race Genotyping Results ...................................................................................................36 

Table 5: Diagnosis Association Analysis Results ..............................................................................40 

Table 6: Diagnosis Genotyping Results ...........................................................................................42 

Supplementary .............................................................................................................................45 

Supplementary File One: PLINK Code ............................................................................................45 

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Mot-clé	Genetics Race Alzheimer's Disease SNPs
Committee Chair / Thesis Advisor	Wharton, Whitney, Emory University
Committee Members	Roesch, Leah, Emory University Scott, Tracy , Emory University

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