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Sex Differences in the Genetic Architecture of Alzheimer’s Disease

  • Logan Dumitrescu
  • Elizabeth Rose Mayeda
  • Kavya Sharman
  • Annah M. Moore
  • Timothy J. HohmanEmail author
Neurogenetics and Psychiatric Genetics (C Cruchaga and C Karch, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Neurogenetics and Psychiatric Genetics

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 of 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 Sex difference Genetics 

Notes

Acknowledgements

This research was supported in part by R01 AG059716 (TJH), K01 AG049164 (TJH), R21 AG05994 (TJH), K12 HD043483 (TJH), HHSN311201600276P (TJH), R00 AG053410 (ERM), and the Vanderbilt Memory & Alzheimer’s Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

Logan Dumitrescu, Kavya Sharman, Annah M. Moore, and Timothy J. Hohman each report an NIH grant. Elizabeth Rose Mayeda reports a grant from the NIA.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Logan Dumitrescu
    • 1
    • 2
  • Elizabeth Rose Mayeda
    • 3
  • Kavya Sharman
    • 1
    • 2
  • Annah M. Moore
    • 1
    • 2
  • Timothy J. Hohman
    • 1
    • 2
    Email author
  1. 1.Vanderbilt Memory and Alzheimer’s CenterVanderbilt University Medical CenterNashvilleUSA
  2. 2.Vanderbilt Genetics Institute, Vanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of Epidemiology, Fielding School of Public HealthUniversity of California Los AngelesLos AngelesUSA

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