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Invited Commentary
October 2016

Using Discordance in Monozygotic Twins to Understand Causality of Cardiovascular Disease Risk Factors

Author Affiliations
  • 1Preventive Cardiology, NorthShore University HealthSystem, Chicago, Illinois
  • 2Lipid Clinic, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois
JAMA Intern Med. 2016;176(10):1530. doi:10.1001/jamainternmed.2016.4115

The risk of developing coronary heart disease (CHD) is determined by both lifestyle and genetics. Previous twin studies1 have indicated that heritable factors may account for as much as 30% to 60% of the variation in risk. Monozygotic twins have identical DNA, but by evaluating discordance in lifestyle-induced changes, such as body weight, this natural experiment can potentially determine whether the long-term impact of obesity is causal for CHD. Just as genome-wide association studies2 have demonstrated causality for low-density lipoprotein cholesterol by demonstrating that lifelong exposure of the surrogate (ie, low-density lipoprotein cholesterol) is associated with greater-than-expected cardiovascular events, a similar understanding regarding lifestyle-stimulated risk factors such as obesity can also be evaluated through capitalizing on differences in body weight between monozygotic twins. The use of this natural experiment implicated cigarette smoking as a major causal factor for increased CHD and mortality. In the Swedish Twins Registry,3 death from CHD was increased 2.8-fold in monozygotic twins who were cigarette smokers compared with the nonsmokers.

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