Molecular genetics & genomic medicine · 2024
Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.
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Wang Qing, Wang Xuehua, Zhuang Qizhen, Wu Yuan, Zhang Junhong, Lu Yue, Wu Jingjing, Liu Juanjuan, Hu Xiangyu, Han Ling
Аннотация
BACKGROUND: Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking.
METHODS: We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.
RESULTS: We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.
CONCLUSIONS: We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.
METHODS: We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.
RESULTS: We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.
CONCLUSIONS: We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.