More Information on the Genetic Link between Psoriasis, Obesity, and Diabetes

Researchers have concluded that there is a small but significant genetic component to the observed connection between high body mass index (BMI) and psoriasis.

A new study of Danish twins concludes that there is a small but significant genetic component to the observed connection between high body mass index (BMI) and psoriasis, the skin condition that often leads to psoriatic arthritis.

Investigators used questionnaire answers and medical records from 33,588 twins to examine correlations between body mass index (BMI), T2DM and psoriasis. The study population, which was 46% male, had a mean age of 44.5 years ± a standard deviation of 7.6 years.

Overall, the study found that psoriasis was nearly twice as common in people with T2DM than in other cohort members (7.6% vs. 4.1%; P =0.001). After adjusting for multiple potential confounders, the investigators found a significant association between psoriasis and T2DM (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03 to 2.27; P =0.4) and between psoriasis and increasing BMI (OR, 1.81; 95% CI, 1.28 to 2.55; P =&thinsp;0.001 in individuals with a BMI>35.0). Overall, the investigators found, patients with psoriasis had slightly larger BMIs than other patients (25 vs 24.4; P <0.001).

Among the study’s 449 psoriasis-discordant twin pairs, the association between psoriasis and obesity was diluted in monozygotic (identical) twins (OR, 1.43; 95% CI, 0.50 to 4.07; P&thinsp;=&thinsp;.50) relative to dizygotic (fraternal) twins (OR, 2.13; 95% CI, 1.03 to 4.39; P&thinsp;=&thinsp;.04). Overall, among those discordant twins, obesity was more common in the twin with psoriasis than the twin with no psoriasis (11.6% vs. 8.1%). After adjusting for potential confounders the twin with psoriasis was almost twice as likely as the other twin to be obese (OR, 1.92; 95% CI, 1.06 to 3.46; P = 0.03)

Variance decomposition showed that additive genetic factors accounted for 68% (95% CI, 60% to 75%) of the variance in the susceptibility to psoriasis, for 73% (95% CI, 58% to 83%) of the variance in susceptibility to T2DM, and for 74% (95% CI, 72% to 76%) of the variance in BMI. The analysis found that the genetic correlation between psoriasis and type T2DM did not reach the level of significance: 0.13 (−0.06 to 0.31; P&thinsp;=&thinsp;.17). The genetic correlation between psoriasis and BMI, on the other hand, was small-but-significant: 0.12 (0.08 to 0.19; P&thinsp;<&thinsp;.001).

The investigators also tried to calculate the impact of environment and found no significant associations. The environmental correlation between psoriasis and T2DM was 0.10 (−0.71 to 0.17; P&thinsp;=&thinsp;.63); The environmental correlation between psoriasis and BMI was −0.05 (−0.14 to 0.04; P&thinsp;=&thinsp;.44).

“This study determines the contribution of genetic and environmental factors to the interaction between obesity, type 2 diabetes mellitus, and psoriasis,” the study authors wrote in JAMA Dermatology. “Psoriasis, type 2 diabetes mellitus, and obesity are also strongly associated in adults after taking key confounding factors, such as sex, age, and smoking, into account. Results indicate a common genetic etiology for psoriasis and obesity.”

The study authors noted that the cross-sectional nature of the study made it impossible to guess whether psoriasis caused obesity — perhaps by making exercise more uncomfortable and encouraging a more sedentary lifestyle — whether obesity caused psoriasis or both conditions stemmed from a common cause.

An accompanying editorial noted that the failure to find a significant genetic component to the association between psoriasis and T2DM says more about the small sample size than the actual existence of any such link (only 6 people in the study had both T2DM and psoriasis).

“These findings are consistent with emerging genetic evidence linking psoriasis to diabetes,” wrote Joel M. Gelfand, MD, the author of the editorial. “For example, genetic variation in IL12B, IL23R, and IL23A has an influence not only on the risk for psoriasis but also on its severity and type 2 diabetes. Other researchers have suggested a role for CDKAL1 in conferring susceptibility to both psoriasis and diabetes.”