Leonie C Jacobs1, Fan Liu2, Isabel Bleyen3, David A Gunn4, Albert Hofman5, Caroline C W Klaver6, André G Uitterlinden7, H A Martino Neumann1, Veronique Bataille8, Timothy D Spector9, Manfred Kayser2, Tamar Nijsten1. 1. Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands. 2. Department of Forensic Molecular Biology, Erasmus Medical Center, Rotterdam, the Netherlands. 3. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. 4. Unilever Research and Development, Colworth Science Park, Sharnbrook, England. 5. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. 6. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands5Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. 7. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands6Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. 8. Department of Twin Research and Genetic Epidemiology, King's College London, London, England8Department of Dermatology, West Hertfordshire Hospitals National Health Service Trust, Hertfordshire, England. 9. Department of Twin Research and Genetic Epidemiology, King's College London, London, England.
Abstract
IMPORTANCE: Sagging eyelids, or dermatochalasis, are a frequent concern in older adults. It is considered a feature of skin aging, but risk factors other than aging are largely unknown. OBJECTIVE: To study nongenetic and genetic risk factors for sagging eyelids. DESIGN: Upper eyelid sagging was graded in 4 categories of severity using digital photographs. Dermatochalasis was defined as the eyelid hanging over the eyelashes. Age, sex, skin color, tanning ability, hormonal status in women, current smoking, body mass index, and sun protection behavior were analyzed in a multivariable multinomial logistic regression model. Genetic predisposition was assessed using heritability analysis and a genome-wide association study. SETTING AND PARTICIPANTS: The study was performed in 2 independent population-based cohorts. The Rotterdam Study included older adults from one district in Rotterdam, the Netherlands, and the UK Adult Twin Registry (TwinsUK) included twins from all over the United Kingdom. Participants were 5578 unrelated Dutch Europeans (mean age, 67.1 years; 44.0% male) from the Rotterdam Study and 2186 twins (mean age, 53.1 years; 10.4% male) from the TwinsUK. MAIN OUTCOMES AND MEASURES: Sagging eyelid severity levels, ranging from 1 (normal control) to 4 (severe sagging). RESULTS: Among 5578 individuals from the Rotterdam Study, 17.8% showed dermatochalasis (moderate and severe sagging eyelids). Significant and independent risk factors for sagging eyelids included age, male sex, lighter skin color, and higher body mass index. In addition, current smoking was borderline significantly associated. Heritability of sagging eyelids was estimated to be 61% among 1052 twin pairs from the TwinsUK (15.6% showed dermatochalasis). A meta-analysis of genome-wide association study results from 5578 Rotterdam Study and 1053 TwinsUK participants showed a genome-wide significant recessive protective effect of the C allele of rs11876749 (P = 1.7 × 10(-8)). This variant is located close to TGIF1 (an inducer of transforming growth factor β), which is a known gene associated with skin aging. CONCLUSIONS AND RELEVANCE: This is the first observational study to date demonstrating that other risk factors (male sex, genetic variants, lighter skin color, high body mass index, and possibly current smoking) in addition to aging are involved in the origin of sagging eyelids.
IMPORTANCE: Sagging eyelids, or dermatochalasis, are a frequent concern in older adults. It is considered a feature of skin aging, but risk factors other than aging are largely unknown. OBJECTIVE: To study nongenetic and genetic risk factors for sagging eyelids. DESIGN: Upper eyelid sagging was graded in 4 categories of severity using digital photographs. Dermatochalasis was defined as the eyelid hanging over the eyelashes. Age, sex, skin color, tanning ability, hormonal status in women, current smoking, body mass index, and sun protection behavior were analyzed in a multivariable multinomial logistic regression model. Genetic predisposition was assessed using heritability analysis and a genome-wide association study. SETTING AND PARTICIPANTS: The study was performed in 2 independent population-based cohorts. The Rotterdam Study included older adults from one district in Rotterdam, the Netherlands, and the UK Adult Twin Registry (TwinsUK) included twins from all over the United Kingdom. Participants were 5578 unrelated Dutch Europeans (mean age, 67.1 years; 44.0% male) from the Rotterdam Study and 2186 twins (mean age, 53.1 years; 10.4% male) from the TwinsUK. MAIN OUTCOMES AND MEASURES: Sagging eyelid severity levels, ranging from 1 (normal control) to 4 (severe sagging). RESULTS: Among 5578 individuals from the Rotterdam Study, 17.8% showed dermatochalasis (moderate and severe sagging eyelids). Significant and independent risk factors for sagging eyelids included age, male sex, lighter skin color, and higher body mass index. In addition, current smoking was borderline significantly associated. Heritability of sagging eyelids was estimated to be 61% among 1052 twin pairs from the TwinsUK (15.6% showed dermatochalasis). A meta-analysis of genome-wide association study results from 5578 Rotterdam Study and 1053 TwinsUK participants showed a genome-wide significant recessive protective effect of the C allele of rs11876749 (P = 1.7 × 10(-8)). This variant is located close to TGIF1 (an inducer of transforming growth factor β), which is a known gene associated with skin aging. CONCLUSIONS AND RELEVANCE: This is the first observational study to date demonstrating that other risk factors (male sex, genetic variants, lighter skin color, high body mass index, and possibly current smoking) in addition to aging are involved in the origin of sagging eyelids.
Authors: Leonie C Jacobs; Merel A Hamer; David A Gunn; Joris Deelen; Jaspal S Lall; Diana van Heemst; Hae-Won Uh; Albert Hofman; André G Uitterlinden; Christopher E M Griffiths; Marian Beekman; P Eline Slagboom; Manfred Kayser; Fan Liu; Tamar Nijsten Journal: J Invest Dermatol Date: 2015-02-23 Impact factor: 8.551
Authors: Felix H W Mak; Michelle Ting; Matthew R Edmunds; Anthony Harker; Mohan Edirisinghe; Sirisha Duggineni; Fabiola Murta; Daniel G Ezra Journal: Plast Reconstr Surg Glob Open Date: 2020-07-21
Authors: Ken Batai; Zuxi Cui; Amit Arora; Ebony Shah-Williams; Wenndy Hernandez; Maria Ruden; Courtney M P Hollowell; Stanley E Hooker; Madhavi Bathina; Adam B Murphy; Carolina Bonilla; Rick A Kittles Journal: PLoS Genet Date: 2021-02-18 Impact factor: 5.917