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Sex Differences in the Genetic Architecture of Alzheimer’s Disease

  • Neurogenetics and Psychiatric Genetics (C Cruchaga and C Karch, Section Editors)
  • Published:
Current Genetic Medicine Reports Aims and scope Submit manuscript

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.

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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.

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  1. Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Logan Dumitrescu, Kavya Sharman, Annah M. Moore & Timothy J. Hohman

  2. Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA

    Logan Dumitrescu, Kavya Sharman, Annah M. Moore & Timothy J. Hohman

  3. Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA

    Elizabeth Rose Mayeda

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Correspondence to Timothy J. Hohman.

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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.

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Dumitrescu, L., Mayeda, E.R., Sharman, K. et al. Sex Differences in the Genetic Architecture of Alzheimer’s Disease. Curr Genet Med Rep 7, 13–21 (2019). https://doi.org/10.1007/s40142-019-0157-1

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