Genetic and environmental factors linked with sagging eyelids

1. Age, male sex, lighter skin color, and high BMI were found to be risk factors for sagging eyelids. 

2. The C allele of rs11876749 on chromosome 18 was protective of dermatochalasis (excess eyelid skin). 

Evidence Rating Level: 2 (Good)            

Study Rundown: Dermatochalasis is a concern for both cosmetic and functional reasons. However, despite its common nature, little is known about predisposing factors to this condition. While previous investigations have shown dermatochalasis is associated with normal aging as well as pathologic conditions (e.g. cutis laxa), few studies have looked at other risk factors for this condition. This study evaluated intrinsic factors, such as heritable traits, as well as extrinsic factors, such as BMI, to evaluate their relationship with sagging eyelids. Authors found that several factors associated with this condition, including: age, male sex, high BMI, lighter skin, and genetic polymorphisms. Strengths of this study were that it looked at two independent populations with a total of 7,764 participants. Limitations included a racially homogenous population with 1.4% of nonwhite twin pairs and the usage of photographs instead of in-person evaluation.

Click to read the study JAMA Dermatology

Relevant Reading: Relative Contribution of Intrinsic vs Extrinsic Factors to Skin Aging as Determined by a Validated Skin Age Score

In-Depth [retrospective cohort]: This study obtained photographs from participants of both the UK Adult Twin registry (TUK; 503 monozygotic pairs, 549 dizygotic pairs and 82 single twins) and the Rotterdam Study (RS; 5578 adults 45 and older). A novel 4-level severity scale was created to rate normal, mild, moderate, and severe sagging. Dermatochalasis was present in 15.6% and 17.8% of the TUK and RS studies, respectively.  In the study of twins, more phenotypic correspondence was found between monozygotic versus dizygotic twins; the variance in sagging due to genetic effect was estimated to be 60.9% while only 2.2% of variance was due to common environmental factors. Three SNPs were found to be significant, all within the same intergenic region of chromosome 18p11 (p values <8.7 x 10-9) Most significantly, rs11876749, a variant near TGIF1, which had previously been implicated in skin aging, was found to be associated with protective effects (C allele, p=1.7 x 10-8).  Extrinsic factors were also associated with dermatochalasis. Male sex was a predictor of moderate and severe sagging (OR 1.22 [95% CI 1.03-1.44], p<.02 and OR 1.70 [95% CI 1.31-2.21], p<.001).  Likewise, increasing age and lighter skin were also risk factors for severe sagging OR 1.38 [1.25-1.52], p <0.001 and OR 1.34 [1.03-1.74]. p=.03], respectively. BMI was associated with mild OR 1.03 [1.01-1.04], p<0.01 and moderate OR 1.02 [1.00-1.04], p=0.04 but not severe sagging.

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