Using statistical genetics to investigate the relationship between stress-related traits and Alzheimer’s disease. — The Association Specialists
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  3. Using statistical genetics to investigate the relationship between stress-related traits and Alzheimer’s disease.

Using statistical genetics to investigate the relationship between stress-related traits and Alzheimer’s disease. (21969)

Ayeisha Milligan Armstrong 1 2 3 4 , Tenielle Porter 1 3 4 , Giuseppe Verdile 1 2 5 , David M Groth 1 2 , Emmanuel O Adewuyi 3 4 , Simon M Laws 1 3 4
  1. Curtin Medical School, Curtin University, Bentley, WA, Australia
  2. Curtin Health Innovation Research Institute, Curtin University , Bentley , WA, Australia
  3. Centre for Precision Health, Edith Cowan University , Joondalup, WA, Australia
  4. Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University , Joondalup, WA, Australia
  5. School of Medical and Health Sciences, Edith Cowan University , Joondalup , WA, Australia

Epidemiological studies have shown that chronic life stress or stress-related disorders such as depression and anxiety are associated with an increased risk of developing Alzheimer’s disease (AD). Underlying mechanisms remain poorly understood. To begin to identify potential biological pathways involved, the study aimed to investigate the shared genetic architecture between stress-related traits (cortisol secretion, stress-response, depression, anxiety and neuroticism scores) and AD-related phenotypes (AD incidence, cognitive measures, hippocampal volume, cerebral spinal fluid (CSF) amyloid-beta (Aβ) and phosphorylated tau levels) using statistical genetic methods. Data from large genome-wide association studies (GWAS) for each of these traits was utilised to explore genome-wide and local genetic correlation in a pair-wise manner (stress-related traits to AD-related traits). Mendelian randomisation was also undertaken to investigate potential causal relationships between stress-related traits and AD-related phenotypes. Finally, gene-level overlap assessments were undertaken to investigate whether there were biological pathways implicated in the risk that were shared between stress-related traits and AD-related phenotypes. A negative global genetic correlation between depression, anxiety and neuroticism with cognition was observed, along with a positive genetic correlation between depression and AD incidence. Local genetic correlation analyses also revealed shared genetic correlations between these traits and allowed for regions of the genome driving these associations to be identified. Finally, at the gene-level, there was significant overlap between neuroticism and AD incidence, cognition and CSF-Αβ. Taken together this study highlights that there is shared genetic architecture with implications in identifying potential biological pathways between stress-related traits and AD-related phenotypes.