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Lifestyle, Genetics Independently Predict Cardiovascular Disease, Diabetes Risk

NEW YORK (GenomeWeb) – New results from the UK Biobank cohort study suggest that lifestyle and genetic factors are independent predictors of cardiovascular disease (CVD) and type 2 diabetes.

"[P]oor behavioral lifestyle was a strong incremental risk factor of new-onset CVD and diabetes in this large cohort," corresponding author Pim van der Harst, a cardiology researcher at the University of Groningen, and his co-authors wrote. They noted that "[genetic risk] and combined health behaviors and factors have a log-additive effect on the risk of new-onset diseases, but there were no interactions between these risk factors."

As they reported online today in JAMA Cardiology, Harst and his colleagues analyzed array-based genotyping profiles and self-reported medication use, disease history, income, and other lifestyle factors from more than 339,000 participants recruited at almost two dozen sites in the UK. They then looked at how well genetic risk and lifestyle factors corresponded to the development of coronary artery disease (CAD), atrial fibrillation (AF), stroke, hypertension, and diabetes over an average of more than six years of follow up.

"To our knowledge, this study is the first to investigate the associations and interactions of combined modifiable health behaviors and factors across [genetic risk] subgroups of CAD, AF, stroke, hypertension, and diabetes simultaneously while adjusting for various demographic confounders," the authors explained.

The researchers began with data for more than 344,000 participants between the ages of 40 and 70, genotyped with custom Affymetrix UK Biobank Axiom arrays. After their quality control steps, they were left with directly genotyped or imputed SNP profiles for up to 339,003 individuals with available genetic, lifestyle, socioeconomic, and disease history data.

The latter group included 157,301 men and 181,702 women, who were followed for 5.5 to 6.7 years. Just over 20 percent of the participants (68,666) had overall lifestyle features classified as ideal, the team noted, while 252,557 were in an intermediate lifestyle group and 17,780 individuals were in a poor lifestyle group.

The investigators did not see specific interactions between the genetic risk and lifestyle factors. Still, there were instances where improved lifestyle seemed to level the playing field somewhat between individuals from different genetic risk groups. In particular, the available data indicated that poor lifestyle can significantly increase the risk of disease development in individuals with enhanced genetic risk of CVD or diabetes.

The team's analyses of CAD risk — based on data for 325,133 of the participants and 9,771 CAD cases — indicated that the absolute CAD risk was highest for individuals with both genetic risk and poor lifestyle, perhaps not surprisingly. In that group, CAD events were more than 4.5-fold as common as they were in individuals with both low genetic risk and an ideal lifestyle.

Such effects were even more pronounced in the case of diabetes. When the researchers considered data for 322,014 individuals, they found that high genetic risk and poor lifestyle coincided with a more than 15-fold rise in diabetes risk, relative to the low genetic risk and ideal lifestyle group.

"For diabetes, the effects of lifestyle on disease development were the strongest," the authors wrote. "Ideal lifestyle returned the risk of incident diabetes toward the referent in any [genetic risk] subgroup, but poor lifestyle was associated with 15-fold higher risk in the high GR group."

Similar large-scale analyses of AF, stroke, and hypertension risk provided a clearer look at the relative contributions that genetic risk and lifestyle factors make to these conditions as well.

In the case of stroke, for example, the team did not see a jump in events in individuals with high genetic risk over those with low genetic risk, at least in the group with ideal lifestyle patterns. But poor lifestyle was linked to almost double the risk of stroke, even in the low genetic risk group.

Based on these and other insights from the new study, the authors suggested that "[b]ehavioral lifestyle changes should be encouraged for all through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on the genetic risk."

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