The British journal of dermatology · 2025
Genomic loci and molecular genetic mechanisms for hidradenitis suppurativa.
СтатьяМетаанализНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Broadaway K Alaine, Sun Quan, Edmiston Sharon N, Currin Kevin W, Vadlamudi Swarooparani, Miller-Fleming Tyne W, Shi Yue, Fajgenbaum Kristen, Melendez-Gonzalez Maria, Bui Helen, Blum Franklin R, Westerkam Linnea, Shams Rayad, Mallela Teja, Levitt Brandt, Lin Lan, Hao Honglin, Memili Aylin, Straub Peter, Zhou Wei, Harris Kathleen Mullan, Martin Alicia, Cox Nancy J, Liu Zhi, Thomas Nancy E, Li Yun, Mohlke Karen L, Sayed Christopher J
Аннотация
BACKGROUND: Hidradenitis suppurativa (HS) is a common, chronic and debilitating inflammatory disease that most commonly affects intertriginous skin. Despite its high heritability, the genetic underpinnings of HS remain poorly understood.
OBJECTIVES: To identify genetic signals associated with HS, determine genetic relationships with other diseases and investigate potential molecular genetic mechanisms.
METHODS: We performed a genome-wide association meta-analysis of six studies, totalling 4540 patients with HS and > 1 million control participants, and identified genetic correlations with other common diseases. We integrated the HS data with expression quantitative trait loci from 10 trait-relevant tissues, epigenomic and transcriptomic data from human scalp, differential expression data from HS lesions vs. adjacent skin and mesenchymal Hi-C chromatin looping data. To identify functional noncoding variants, we performed transcriptional reporter assays for signals near KLF5 and SOX9.
RESULTS: We identified 11 significant HS signals across 7 loci: 4 corresponded to previously reported associations, 4 represented novel signals within known loci and 3 were signals in newly implicated loci. We identified significant genetic correlations between HS and other inflammatory conditions, particularly inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes mellitus and asthma. We prioritized candidate genes for the 11 signals. The risk allele at KLF5 exhibited 10-fold greater transcriptional activity than the nonrisk allele, while risk alleles at SOX9 showed significantly reduced transcriptional activity.
CONCLUSIONS: Our results provide insights into potential genetic mechanisms underlying HS and suggest potential therapeutic targets for this challenging condition.
OBJECTIVES: To identify genetic signals associated with HS, determine genetic relationships with other diseases and investigate potential molecular genetic mechanisms.
METHODS: We performed a genome-wide association meta-analysis of six studies, totalling 4540 patients with HS and > 1 million control participants, and identified genetic correlations with other common diseases. We integrated the HS data with expression quantitative trait loci from 10 trait-relevant tissues, epigenomic and transcriptomic data from human scalp, differential expression data from HS lesions vs. adjacent skin and mesenchymal Hi-C chromatin looping data. To identify functional noncoding variants, we performed transcriptional reporter assays for signals near KLF5 and SOX9.
RESULTS: We identified 11 significant HS signals across 7 loci: 4 corresponded to previously reported associations, 4 represented novel signals within known loci and 3 were signals in newly implicated loci. We identified significant genetic correlations between HS and other inflammatory conditions, particularly inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes mellitus and asthma. We prioritized candidate genes for the 11 signals. The risk allele at KLF5 exhibited 10-fold greater transcriptional activity than the nonrisk allele, while risk alleles at SOX9 showed significantly reduced transcriptional activity.
CONCLUSIONS: Our results provide insights into potential genetic mechanisms underlying HS and suggest potential therapeutic targets for this challenging condition.