Genetic Study Strengthens Causal Role of BMI in Heart Disease

July 07, 2017 – A new study analyzing genetic mutations predisposing to increased body-mass index (BMI) provides strong evidence that higher BMI plays a causal role in type 2 diabetes, hypertension, and coronary heart disease (CHD). The study results strongly suggest that BMI is causally related to increased risk of developing diabetes, hypertension, and CHD if you are born with certain variants of genes that tend to increase your BMI.

The current study used an approach known as a Mendelian randomization (see here for explanation), often referred to as nature’s own randomized study, which focuses on certain gene mutations known to be associated with a given variable, in this case, BMI, and their relationship to certain outcomes, in this case, diabetes, hypertension, and CHD.

For the study, researchers analyzed genetic, medical, and sociodemographic information from 120,000 individuals included in the UK Biobank. A polygenic risk score comprising 93 single-nucleotide polymorphisms (SNP’s)  associated with BMI from previous genomewide association studies was constructed. All participants attended an assessment center where blood pressure was measured and prevalence of hypertension, CHD, and type 2 diabetes were determined based on self-report. Participants also self-reported sociodemographic information pertaining to relevant confounders.

Using the genetic data, results showed that each 4.8-unit increase in BMI was associated with a 35% increased risk of CHD (odds ratio [OR] 1.35; 95% CI 1.09–1.69); a 64% increased risk of hypertension (OR 1.64; 95% CI 1.48–1.83); and a 153% increased risk of type 2 diabetes (OR 2.53; 95% CI 2.0–43.13). However, no associations with pulse rate or stroke were identified. Associations were independent of deprivation scores, alcohol intake, smoking status, age, sex, and antihypertensive medication.

In an accompanying editor’s note, JAMA’s associate editor Dr Christopher J O’Donnell pointed out that in well-established cohorts, BMI has clearly been associated with both traditional risk factors and CHD, but the association of BMI with CHD was found nonsignificant after adjustment for other major modifiable risk factors. The current Mendelian randomization study however refocuses attention on and strengthens the body of evidence / literature for a causal connection of BMI with increasing blood pressure, diabetes, and CHD at least in individuals that carry (the) according genetic disposition(s).

Still further research may be needed to expand the fully understanding the molecular mechanisms that lead  to the observed clinical phenotypes and to further understand which subgroups of individuals are carrying the highest genetically determined risks. For patients, it would be most informative which one(s) of the 93 SNP’s examined carries the highest risk(s) for the clinical endpoints discussed in the present study and how these risk could reasonably be dealt with in real life.



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About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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