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. 2023 Jan 30:13:1072573.
doi: 10.3389/fimmu.2022.1072573. eCollection 2022.

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Yicheng Li  1 , Shuting Yang  2 , Minjun Liao  3 , Zijun Zheng  1 , Mengyao Li  1 , Xuerong Wei  1 , Mengqian Liu  1 , Lei Yang  1
Affiliations

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Yicheng Li et al. Front Immunol. .

Abstract

Background: The most commonly acknowledged non-scarring alopecia are androgenetic alopecia (AGA) and alopecia areata (AA). Previous studies have revealed various risk factors associated with alopecia. However, the relationship between leukocyte telomere length (LTL) and non-scarring alopecia remains unclear.

Methods: A two-sample Mendelian randomization (MR) analysis was performed to evaluate the causality between genetically predicted LTL and the risk of non-scarring alopecia. MR analyses were performed using the inverse variance-weighted (IVW) method and complemented with other MR methods.

Results: The summary statistics of the genome-wide association studies (GWAS) for AGA and AA were obtained from the FinnGen biobank, which included 119,185 and 211,428 individuals, respectively. A total of 126 single nucleotide polymorphisms (SNPs) with genome-wide significance were selected as the instrumental variables for LTL. The MR analyses suggested a causal relationship between LTL and AGA, and the risk of AGA increased by 3.19 times as the genetically predicted LTL was shortened by one standard deviation in log transformed form under the IVW method (OR = 4.19, 95% CI = 1.20-14.61, p = 0.024). The other MR methods also demonstrated a similar trend of the effect of LTL on AGA. There was no causal relationship between LTL and AA (p > 0.05). Sensitivity analyses further demonstrated that the current results were less likely to be affected by confounders and bias.

Conclusion: Our results suggested a potential causal relationship between LTL and AGA, and shortened LTL was associated with an increased risk of AGA.

Keywords: Mendelian randomization; alopecia areata; androgenetic alopecia; leukocyte telomere length; non-scarring alopecia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Detailed flowchart of the current two-sample Mendelian randomization study. (B) Mendelian randomization assumptions. GWAS, genome-wide summary association study; LTL, leukocyte telomere length; AGA, androgenetic alopecia; AA, alopecia areata; SNP, single nucleotide polymorphism; MR, Mendelian randomization; MR-Egger, Mendelian randomization-Egger; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier.
Figure 2
Figure 2
Scatter plots for the effects of single-nucleotide polymorphisms (SNPs) on telomere length and non-scarring alopecia. The x-axis represents the effects of each genetic variant on telomere length, and the y-axis represents the effects of each genetic variant on androgenetic alopecia (A) or alopecia areata (B).
Figure 3
Figure 3
Funnel plots of leukocyte telomere length genetic variants and non-scarring alopecia. (A, B). Funnel plots for androgenetic alopecia (A) and alopecia areata (B).
Figure 4
Figure 4
Forest plot of the association between genetically predicted telomere length and androgenetic alopecia. OR refers to the change of alopecia risk associated with a one standard deviation (SD) decrease in telomere length. IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval.
Figure 5
Figure 5
Forest plot of the association between genetically predicted telomere length and alopecia areata.
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