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Original Investigation |

Genetic vs Environmental Factors That Correlate With Rosacea A Cohort-Based Survey of Twins

Nely Aldrich, MD1; Meg Gerstenblith, MD1; Pingfu Fu, PhD2; Marie S. Tuttle, MD1; Priya Varma, BS1; Erica Gotow, BS1; Kevin D. Cooper, MD1; Margaret Mann, MD1; Daniel L. Popkin, MD, PhD1,3,4
[+] Author Affiliations
1Department of Dermatology, University Hospitals Case Medical Center, Cleveland, Ohio
2Department of Epidemiology & Biostatistics, University Hospitals Case Medical Center, Cleveland, Ohio
3Department of Pathology, Case Western Reserve University, Cleveland, Ohio
4Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio
JAMA Dermatol. 2015;151(11):1213-1219. doi:10.1001/jamadermatol.2015.2230.
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Importance  To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions.

Objectives  To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility.

Design, Setting, and Participants  Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated.

Main Outcomes and Measures  The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists.

Results  Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P < .001) and lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (r = 0.21; P < .001), smoking (r = 0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P < .001).

Conclusions and Relevance  The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

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Figure 1.
Identical Twins Discordant for Rosacea

Twins are considered concordant when both express the same phenotype and discordant when only one expresses that phenotype.

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Figure 2.
National Rosacea Society (NRS) Score in Identical vs Fraternal Twins and Correlation With Demographic Factors

A, A genetic contribution is supported by the higher correlation of the NRS scores between 2 identical twins than 2 fraternal twins. For identical and fraternal twins, each triangle and circle represents a set of twins. Triangle indicates fraternal; circle, identical. B, There was a correlation between NRS score and age, UV radiation exposure, body mass index (calculated as weight in kilograms divided by height in meters squared), skin cancer comorbidity, and cardiovascular comorbidity. Weaker associations included adjusted pack-years and alcohol consumption. All analyses were univariate.

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