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. 2019 Mar;7(1):13-21.
doi: 10.1007/s40142-019-0157-1. Epub 2019 Jan 21.

Sex Differences in the Genetic Architecture of Alzheimer's Disease

Logan Dumitrescu  1   2 , Elizabeth Rose Mayeda  3 , Kavya Sharman  1   2 , Annah M Moore  1   2 , Timothy J Hohman  1   2
Affiliations

Sex Differences in the Genetic Architecture of Alzheimer's Disease

Logan Dumitrescu et al. Curr Genet Med Rep. 2019 Mar.

Abstract

Purpose of review: Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD).

Recent findings: There are sex differences in the effects of Apolipoprotein E (APOE), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD.

Summary: There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting a sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.

Keywords: Alzheimer disease; Genetics; Sex difference.

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Conflict of interest statement

Conflict of Interest Logan Dumitrescu, Kavya Sharman, Annah M. Moore, and Timothy J. Hohman each report an NIH grant.

Figures

Figure 1:
Figure 1:. Hypothesized Emergence of Sex-Specific Drivers of AD.
We posit that sex differences in the genetic drivers of AD largely emerge downstream of amyloidosis. Top Arrow: Female-specific genetic effects. Middle Arrow: Shared genetic effects; Bottom Arrow: Male-specific genetic effects. Width of Arrow: Effect size.
See this image and copyright information in PMC

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