Genetic association of lipid and lipid-lowering drug target genes with atopic dermatitis: a drug target Mendelian randomization study

作者全名："Niu, Qinwang; Zhang, Tongtong; Mao, Rui; Zhao, Nana; Deng, Sui"

作者地址："[Niu, Qinwang] Sichuan Polytech Univ, Deyang 618000, Peoples R China; [Zhang, Tongtong; Zhao, Nana] Chongqing Med Univ, Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Med Res Ctr,Affiliated Hosp,Chengdu Hosp Affiliate, Chengdu 610031, Sichuan, Peoples R China; [Mao, Rui] Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha, Peoples R China; [Deng, Sui] Cent South Univ, Changde Hosp, Peoples Hosp Changde City 1, Xiangya Sch Med, Changde, Peoples R China"

通信作者："Mao, R (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha, Peoples R China.; Deng, S (通讯作者)，Cent South Univ, Changde Hosp, Peoples Hosp Changde City 1, Xiangya Sch Med, Changde, Peoples R China."

来源：SCIENTIFIC REPORTS

ESI学科分类：Multidisciplinary

WOS号：WOS:001284942100021

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Atopic dermatitis; Serum lipid; Mendelian randomization; Genome-wide association study; Beta nerve growth factor; Proprotein convertase subtilisin/kexin type 9

摘要："Observational studies suggest dyslipidemia as an atopic dermatitis (AD) risk factor and posit that lipid-lowering drugs may influence AD risk, but the causal link remains elusive. Mendelian randomization was applied to elucidate the causal role of serum lipids in AD and assess the therapeutic potential of lipid-lowering drug targets. Genetic variants related to serum lipid traits and lipid-lowering drug targets were sourced from the Global Lipid Genetics Consortium GWAS data. Comprehensive AD data were collated from the UK Biobank, FinnGen, and Biobank Japan. Colocalization, Summary-data-based Mendelian Randomization (SMR), and mediation analyses were utilized to validate the results and pinpoint potential mediators. Among assessed targets, only Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) was significantly linked to a reduced AD risk, corroborated across three separate AD cohorts. No association between serum lipid concentrations or other lipid-lowering drug targets and diminished AD risk was observed. Mediation analysis revealed that beta nerve growth factor (b-NGF) might mediate approximately 12.8% of PCSK9's influence on AD susceptibility. Our findings refute dyslipidemia's role in AD pathogenesis. Among explored lipid-lowering drug targets, PCSK9 stands out as a promising therapeutic agent for AD."

基金机构：Global Lipids Genetics Consortium

基金资助正文："We extend our profound gratitude to the researchers who generously shared their Genome-Wide Association Study data, making this investigation possible. We are especially thankful to the participants and dedicated teams behind the UK Biobank, FinnGen consortium, Biobank Japan, and the Global Lipids Genetics Consortium. Their commitment to advancing science and contributing invaluable resources has been instrumental in driving this research forward."