AURORA, CO — Height appears to be an unrecognized non-modifiable risk factor for several common conditions in adults, according to a study using data from the VA Million Veteran Program.
Background information in the report in PloS Genetics recounted how adult height has been associated with a range of clinical traits, including increased risk of atrial fibrillation and with decreased risk of cardiovascular disease.
Researchers from the VA Eastern Colorado Health Care System and the University of Colorado Anschutz Medical Campus, both in Aurora, CO, and colleagues used data from the VA Million Veteran Program that includes genetic data linked to clinical records in more than 200,000 non-Hispanic white adults and more than 50,000 non-Hispanic Black adults.
The study team assessed the associations of measured height and genetically-predicted height with clinical traits phenome-wide.
“By comparing associations of traits with measured and with genetically-predicted height, we aimed to discriminate between potentially causal associations (those associated with genetically-predicted height) from associations that may be confounded by environmental exposures over the life course (those associated with measured height but not with genetically-predicted height),” they explained.
The authors added, “Of approximately 350 traits associated with measured height, we found 127 associated with genetically-predicted height in non-Hispanic white individuals. While only two were also statistically significant in non-Hispanic Black individuals, we found evidence for consistent directions of effect for associations of traits with genetically-predicted height in non-Hispanic Black and white individuals.”
For the Mendelian Randomization-Phenome-wide association study (MR-PheWAS), researchers analyzed the data, estimating height genetic risk based on 3,290 height-associated variants from a recent European-ancestry genome-wide meta-analysis.
Associations were largely independent of body mass index, the authors explained, stating that they confirmed several previously described MR associations between height and cardiovascular disease traits such as:
- hypertension,
- hyperlipidemia,
- coronary heart disease (CHD), and
- atrial fibrillation.
The also uncovered possible associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes.
“As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD,” the study noted. “We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders.”
The authors concluded that that height might be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.
- Raghavan S, Huang J, Tcheandjieu C, Huffman JE, et. al. A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program. PLoS Genet. 2022 Jun 2;18(6):e1010193. doi: 10.1371/journal.pgen.1010193. PMID: 35653334; PMCID: PMC9162317.
