This study evaluates the association between testosterone levels and risk of dementia and adverse mental health outcomes (e.g. depression and anxiety). It is not known whether low testosterone levels may be associated with an increased risk of dementia. Learning about the association between testosterone levels and risk of dementia may help determine the long-term effects of androgen deprivation therapy and may help improve quality of life.
PRIMARY OBJECTIVE: I. To use a Mendelian randomization study design to determine whether genetically predicted decreased testosterone levels are associated with an increased risk of dementia. SECONDARY OBJECTIVE: I. To examine whether genetically predicted decreased testosterone levels are associated with worse cognitive function and adverse mental health outcomes. OUTLINE: Patients' records from institutional or national biobanks are reviewed.
Study Type
OBSERVATIONAL
Enrollment
700,000
Biobank records are reviewed
M D Anderson Cancer Center
Houston, Texas, United States
RECRUITINGAssociation between germline genetic predictors (single nucleotide variants) of lower testosterone levels and dementia risk
Will utilize genetic variants associated with testosterone levels at genome-wide statistical significance thresholds (P \< 5 x 10-8) in published meta-analyses. Will additionally conduct a genome-wide association study with testosterone values in the UK Biobank. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Time frame: Up to 2 years
Depression
Association between low testosterone levels and depression will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Time frame: Up to 2 years
Anxiety
Association between low testosterone levels and anxiety will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Time frame: Up to 2 years
Cognitive/mental health
Association between low testosterone levels and cognitive/mental health will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Time frame: Up to 2 years
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