Genetic factors are stressed variably by onset age‐based sample selection in psoriasis: A hint from major histocompatibility complex region‐based analysis

Ye, Lei; Yang, Chao; Dou, Jinfa; Wen, Leilei; Wang, Wenjun; Zheng, Xiaodong; Zuo, Xianbo; Zhou, Fusheng; Fan, Xing; Zhang, Xuejun

doi:10.1002/jgm.2997

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References 31 publications

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“…We constructed a Han-MHC database and identified eight independent susceptibility loci associated with psoriasis, including HLA-C * 06:02, amino acids at positions 9 and 67 in HLA-B, HLA-C * 07:04, rs118179173, amino acid at position 116 in HLA-B, DPB1 * 05:01, and amino acid at position 281 in BTNL2 9 . Moreover, by analyzing genetic associations between psoriasis subphenotypes divided by age of onset and shared control subjects, our group found that the number of susceptible variants decreased as the onset age of psoriasis increased 10 . In addition, several other genetic studies have reported that HLA-C * 06 is more strongly associated with EOP in various races 11 .…”

Section: Introductionmentioning

confidence: 99%

A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and Late-Onset Psoriasis in China

et al. 2021

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Background Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP; <40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C * 06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods We first calculated the MHC-based heritability of EOP and LOP respectively. Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previous study. Results We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%). Further association analysis identified three independent loci (HLA-C * 01:02, p =6.70×10 −8 ; HLA-A amino acid position 9, p =3.27×10 −17 ; and HLA-A amino acid position 161, p =5.75×10 −10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C * 06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C * 06:02-positive psoriasis patients have earlier onset. Conclusion Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

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Section: Introductionmentioning

confidence: 99%

A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and Late-Onset Psoriasis in China

et al. 2021

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Genetic factors are stressed variably by onset age‐based sample selection in psoriasis: A hint from major histocompatibility complex region‐based analysis

Abstract: Onset age-based sample variables influence the results of genetic association studies, at least in MHC region-based genetic analysis. We suggest that caution is required when selecting samples for genetic association studies to prevent confounders that might be a result of onset age.

Cited by 1 publication

References 31 publications

A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and Late-Onset Psoriasis in China

A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and Late-Onset Psoriasis in China

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