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Invited Commentary |

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

David J. Davidson, MD1; Michael H. Davidson, MD2
[+] Author Affiliations
1Preventive Cardiology, NorthShore University HealthSystem, Chicago, Illinois
2Lipid Clinic, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois
JAMA Intern Med. Published online August 01, 2016. doi:10.1001/jamainternmed.2016.4115
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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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