Ann Sophie Lønnberg1, Lone Skov1, Axel Skytthe2, Kirsten Ohm Kyvik3, Ole Birger Pedersen4, Simon Francis Thomsen5. 1. Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 2. The Danish Twin Registry, Institute of Regional Health Services Research, University of Southern Denmark, Odense. 3. Odense Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark. 4. Department of Clinical Immunology, Naestved Hospital, Naestved, Denmark. 5. Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark6Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
IMPORTANCE: Psoriasis has been shown to be associated with overweight and type 2 diabetes mellitus. The genetic association is unclear. OBJECTIVE: To examine the association among psoriasis, type 2 diabetes mellitus, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in twins. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, population-based twin study included 34 781 Danish twins, 20 to 71 years of age. Data from a questionnaire on psoriasis was validated against hospital discharge diagnoses of psoriasis and compared with hospital discharge diagnoses of type 2 diabetes mellitus and self-reported BMI. Data were collected in the spring of 2002. Data were analyzed from January 1 to October 31, 2014. MAIN OUTCOMES AND MEASURES: Crude and adjusted odds ratios (ORs) were calculated for psoriasis in relation to type 2 diabetes mellitus, increasing BMI, and obesity in the whole population of twins and in 449 psoriasis-discordant twins. Variance component analysis was used to measure genetic and nongenetic effects on the associations. RESULTS: Among the 34 781 questionnaire respondents, 33 588 with complete data were included in the study (15 443 men [46.0%]; 18 145 women [54.0%]; mean [SD] age, 44.5 [7.6] years). After multivariable adjustment, a significant association was found between psoriasis and type 2 diabetes mellitus (odds ratio [OR], 1.53; 95% CI, 1.03-2.27; P = .04) and between psoriasis and increasing BMI (OR, 1.81; 95% CI, 1.28-2.55; P = .001 in individuals with a BMI>35.0). Among psoriasis-discordant twin pairs, the association between psoriasis and obesity was diluted in monozygotic twins (OR, 1.43; 95% CI, 0.50-4.07; P = .50) relative to dizygotic twins (OR, 2.13; 95% CI, 1.03-4.39; P = .04). Variance decomposition showed that additive genetic factors accounted for 68% (95% CI, 60%-75%) of the variance in the susceptibility to psoriasis, for 73% (95% CI, 58%-83%) of the variance in susceptibility to type 2 diabetes mellitus, and for 74% (95% CI, 72%-76%) of the variance in BMI. The genetic correlation between psoriasis and type 2 diabetes mellitus was 0.13 (-0.06 to 0.31; P = .17); between psoriasis and BMI, 0.12 (0.08 to 0.19; P < .001). The environmental correlation between psoriasis and type 2 diabetes mellitus was 0.10 (-0.71 to 0.17; P = .63); between psoriasis and BMI, -0.05 (-0.14 to 0.04; P = .44). CONCLUSIONS AND RELEVANCE: This study determines the contribution of genetic and environmental factors to the interaction between obesity, type 2 diabetes mellitus, and psoriasis. 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.
IMPORTANCE: Psoriasis has been shown to be associated with overweight and type 2 diabetes mellitus. The genetic association is unclear. OBJECTIVE: To examine the association among psoriasis, type 2 diabetes mellitus, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in twins. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, population-based twin study included 34 781 Danish twins, 20 to 71 years of age. Data from a questionnaire on psoriasis was validated against hospital discharge diagnoses of psoriasis and compared with hospital discharge diagnoses of type 2 diabetes mellitus and self-reported BMI. Data were collected in the spring of 2002. Data were analyzed from January 1 to October 31, 2014. MAIN OUTCOMES AND MEASURES: Crude and adjusted odds ratios (ORs) were calculated for psoriasis in relation to type 2 diabetes mellitus, increasing BMI, and obesity in the whole population of twins and in 449 psoriasis-discordant twins. Variance component analysis was used to measure genetic and nongenetic effects on the associations. RESULTS: Among the 34 781 questionnaire respondents, 33 588 with complete data were included in the study (15 443 men [46.0%]; 18 145 women [54.0%]; mean [SD] age, 44.5 [7.6] years). After multivariable adjustment, a significant association was found between psoriasis and type 2 diabetes mellitus (odds ratio [OR], 1.53; 95% CI, 1.03-2.27; P = .04) and between psoriasis and increasing BMI (OR, 1.81; 95% CI, 1.28-2.55; P = .001 in individuals with a BMI>35.0). Among psoriasis-discordant twin pairs, the association between psoriasis and obesity was diluted in monozygotic twins (OR, 1.43; 95% CI, 0.50-4.07; P = .50) relative to dizygotic twins (OR, 2.13; 95% CI, 1.03-4.39; P = .04). Variance decomposition showed that additive genetic factors accounted for 68% (95% CI, 60%-75%) of the variance in the susceptibility to psoriasis, for 73% (95% CI, 58%-83%) of the variance in susceptibility to type 2 diabetes mellitus, and for 74% (95% CI, 72%-76%) of the variance in BMI. The genetic correlation between psoriasis and type 2 diabetes mellitus was 0.13 (-0.06 to 0.31; P = .17); between psoriasis and BMI, 0.12 (0.08 to 0.19; P < .001). The environmental correlation between psoriasis and type 2 diabetes mellitus was 0.10 (-0.71 to 0.17; P = .63); between psoriasis and BMI, -0.05 (-0.14 to 0.04; P = .44). CONCLUSIONS AND RELEVANCE: This study determines the contribution of genetic and environmental factors to the interaction between obesity, type 2 diabetes mellitus, and psoriasis. 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.
Authors: Micah Belzberg; Martin Prince Alphonse; Isabelle Brown; Kyle A Williams; Raveena Khanna; Byron Ho; Shannon Wongvibulsin; Thomas Pritchard; Youkyung Sophie Roh; Nishadh Sutaria; Justin Choi; Jaroslaw Jedrych; Andrew D Johnston; Kakali Sarkar; Chirag Vasavda; Jimmy Meixiong; Carly Dillen; Kent Bondesgaard; John F Paolini; Wei Chen; David Corcoran; Nicolas Devos; Madan M Kwatra; Anna L Chien; Nathan K Archer; Luis A Garza; Xinzhong Dong; Sewon Kang; Shawn G Kwatra Journal: J Invest Dermatol Date: 2021-03-23 Impact factor: 7.590
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