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A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program
Sridharan Raghavan1,2, Jie Huang3, Catherine Tcheandjieu4,5
1Medicine Service, Veterans Affairs Eastern Colorado Health Care System, Aurora, Colorado, United States of America.
Plos Genetics
|June 2, 2022
Summary
Height may be a risk factor for common adult conditions. Mendelian Randomization-Phenome-wide association studies (MR-PheWAS) identified 127 traits linked to genetically predicted height, largely independent of body mass index.
Area of Science:
- Human genetics
- Complex disease epidemiology
- Statistical genetics
Background:
- Height is linked to clinical traits, but causal relationships are often unclear.
- Systematic investigation of height's causal associations with health outcomes is needed.
Purpose of the Study:
- To systematically examine the causal associations between height and clinical traits using Mendelian Randomization-Phenome-wide association study (MR-PheWAS).
Main Methods:
- Utilized clinical and genetic data from the US Veterans Affairs (VA) Million Veteran Program.
- Estimated height genetic risk using 3290 height-associated variants.
- Compared associations of measured and genetically-predicted height with phenome-wide traits from electronic health records.
Main Results:
- Identified 345 traits associated with measured height and 127 traits with genetically-predicted height in non-Hispanic White adults.
- Found largely independent associations from body mass index.
- Confirmed height associations with cardiovascular diseases and uncovered links to venous circulatory disorders and peripheral neuropathy.
Conclusions:
- Height may be an unrecognized risk factor for several common adult conditions.
- Further research is required to rule out horizontal pleiotropy in observed Mendelian Randomization associations.
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