Obesity, Glycemic Traits, Lifestyle Factors, and Risk of Facial Aging: A Mendelian Randomization Study in 423,999 Participants

Abstract

Background: Several recent observational studies have associated obesity, lifestyle factors (smoking, sleep duration, and alcohol drinking), and glycemic traits with facial aging. However, whether this relationship is causal due to confounding and reverse causation is yet to be substantiated.

Aims: We aimed to assess these relationships using Mendelian randomization (MR).

Methods: For the instrumental variables, this paper selected independent single nucleotide polymorphisms (SNPs) linked to the exposures at a genome-wide state (P < 5 × 10-8) in equivalent genome-wide association studies (GWAS). Using the UK Biobank, we obtained summary-level data for facial aging on 423,999 individuals. The primary assessments were performed through the combination of complementing techniques (simple method approaches, weighted model, MR-Egger, and weighted median) and the inverse-variance-weighted method. Along with that, we examined the heterogeneity and horizontal pleiotropy through different types of sensitivity analyses.

Results: The correlations were (a) facial aging for body mass index (BMI, OR = 1.054, 95% CI 1.044-1.64), (b) waist/hip ratio (OR = 1.056, 95% CI 1.023-1.091), and (c) smoking (OR = 1.023, 95% CI 1.007-1.039). Equally important, the correlations for waist/hip ratio remained robust after adjusting for the genetically predicted BMI (OR = 1.028, 95% CI 1.003-1.054). However, no causal effects of alcoholic drinking, glycemic traits, and sleep duration on facial aging were observed.

Conclusions: The outcomes shed light on the potential correlation of obesity and cigarette smoking with facial aging while putting forward a more comprehensive and credible foundation for the optimization of facial aging strategies.

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Keywords: Facial aging; Glycemic traits; Lifestyle factors; Mendelian randomization study; Obesity.