Anxiety Disorder, Depression, Genetic Disorder, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Conditions
Brief summary
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.
Detailed description
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.
Interventions
OTHERElectronic Health Record Review
Biobank records are reviewed
Sponsors
M.D. Anderson Cancer Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Have volunteered to participate in institutional or national biobanks, mainly the UK Biobank and the Kaiser Permanente Research Bank, and those that have previously participated in studies that resulted in de-identified clinical and genetic data being make available on public archives, mainly the database of Genotypes and Phenotypes (dbGaP) * No special populations (adults unable to consent, individuals not yet adults, pregnant women, or prisoners)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Association between germline genetic predictors (single nucleotide variants) of lower testosterone levels and dementia risk | Up to 2 years | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression | Up to 2 years | 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). |
| Anxiety | Up to 2 years | 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). |
| Cognitive/mental health | Up to 2 years | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKevin Nead
M.D. Anderson Cancer Center
Outcome results
None listed