Evidence map›Paper›PMID 41398807›Full record

ArticleMedicine2025

Causal effects of glutamine and lipid-related metabolites on alopecia areata: A 2-sample Mendelian randomization study.

Xiao-Shuang Yang, Ru Dai, Yu-Jie Miao, Sheng-Zhao Chen, Zhong-Fa Lv

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Article in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Xiao-Shuang YangDepartment of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China.
Ru Dai
Yu-Jie Miao
Sheng-Zhao Chen
Zhong-Fa Lv

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alopecia areata (AA) is an autoimmune hair loss disorder that affects approximately 2% of the global population, imposing a substantial psychological burden and impairing the quality of life. Although observational studies have correlated blood metabolites with AA, these associations are susceptible to confounding and reverse causality, leaving the causal direction unclear. This study employed a 2-sample Mendelian randomization (MR) approach to infer the causal relationship between blood metabolites and AA. This study used publicly available genome-wide association study summary statistics for blood metabolites (Kettunen et al, N = 24,925) and AA (FinnGen, 682 cases/361,140 controls), both based on European ancestry populations. Single-nucleotide polymorphisms significantly associated with metabolites were selected as instrumental variables, while those in linkage disequilibrium or with an F-statistic < 10 were excluded to ensure the robustness of the instruments. The primary analysis utilized the inverse variance weighted method, supplemented by MR-Egger, weighted median, and MR-PRESSO analyses to assess horizontal pleiotropy and heterogeneity. A leave-one-out sensitivity analysis was performed to evaluate the influence of individual single-nucleotide polymorphisms. Forward MR analysis identified 25 blood metabolites suggesting potential causal effects on AA. Specifically, glutamine exhibited a protective effect (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.35-0.99). Positive associations were observed for the ratio of free cholesterol to cholesterol esters (OR = 1.34, 95% CI: 1.04-1.74), serum total cholesterol (OR = 1.31, 95% CI: 1.02-1.68), citric acid (OR = 2.89, 95% CI: 1.41-5.92), and glucose (OR = 1.99, 95% CI: 1.01-3.92). Notably, lipoprotein-related metabolites accounted for the majority of significant findings (80%; 20/25). Reverse MR analysis did not support reverse causality. Sensitivity analyses confirmed the robustness of these associations, with no significant horizontal pleiotropy or heterogeneity detected. Our study suggests potential causal associations between blood levels of glutamine, citric acid, glucose, various lipids, and lipoproteins with AA. Initial analyses found no evidence of reverse causality. These findings require further investigation for validation.

Indexed as

Alopecia AreataGlutamineLipidsGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideGlutamineLipidsalopecia areatablood metaboliteshair follicleMendelian randomization study

Identifiers

PMID41398807
PMCPMC12708083

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.