title: Intrinsic and extrinsic risk factors for sagging eyelids.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.affiliation: Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Leonie C
authors.initials: LC
authors.lastname: Jacobs
authors.affiliation: Department of Forensic Molecular Biology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Isabel
authors.initials: I
authors.lastname: Bleyen
authors.affiliation: Unilever Research and Development, Colworth Science Park, Sharnbrook, England.
authors.forename: David A
authors.initials: DA
authors.lastname: Gunn
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands5Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands6Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: H A Martino
authors.initials: HA
authors.lastname: Neumann
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, England8Department of Dermatology, West Hertfordshire Hospitals National Health Service Trust, Hertfordshire, England.
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, England.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Forensic Molecular Biology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
authors.affiliation: Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Tamar
authors.initials: T
authors.lastname: Nijsten
mesh_terms: D000367:Age Factors; D000368:Aged; D001763:Blepharoptosis / Q000145:classification / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study; D005838:Genotype; D015438:Health Behavior; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D015595:Skin Aging; D012880:Skin Pigmentation; D012907:Smoking / Q000453:epidemiology; D013472:Sunlight; D018433:Twin Studies as Topic; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human