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

• Published in: The journal of gene medicine Vol. 19; no. 12
• Main Authors: Ye, Lei, Yang, Chao, Dou, Jin‐Fa, Wen, Lei‐Lei, Wang, Wen‐Jun, Zheng, Xiao‐Dong, Zuo, Xian‐Bo, Zhou, Fu‐Sheng, Fan, Xing, Zhang, Xue‐Jun
• Format: Journal Article
• Language: English
• Published: England Wiley Periodicals Inc 01.12.2017
• Subjects: Adolescent; Adult; Age; Age of Onset; Aged; Aged, 80 and over; Association analysis; Child; Child, Preschool; Female; Gene therapy; Genetic analysis; Genetic Association Studies - methods; Genetic factors; Genome-wide association studies; Genomes; Histocompatibility antigen HLA; Humans; Infant; Major histocompatibility complex; Major Histocompatibility Complex - genetics; Male; Middle Aged; Minority & ethnic groups; onset age; Polymorphism, Single Nucleotide; precision genetics; Psoriasis; Psoriasis - genetics; Regression Analysis; Studies; Young Adult; precision genetics; major histocompatibility complex; onset age; psoriasis
• DOI: 10.1002/jgm.2997
• ISSN: 1099-498X; 1521-2254

Background Large cohort‐based genetic association studies have been established over a decade. However, for certain diseases, different results with respect to the genome‐wide association study level have been obtained among studies, even for those conducted within the same ethnic groups. We hypothesized that onset age‐based sample variables might have a great impact on the results. Methods In the present study, we divided psoriasis patients into several subgroups according to the onset age bracket. We conducted genetic association analysis in the major histocompatibility complex (MHC) region of each patient subgroup with shared control subjects. Results We found decreases in the numbers of susceptible variants in each subgroup analysis as the onset age increased in the longitudinal analysis. Meanwhile, the pairwise analysis showed that younger patients exhibited greater numbers of genetic risks in the MHC region compared to elder patients, regardless of whether the cut‐off values were defined as 20 or 30 years old. Similar results were also found among 11–20‐, 21–30‐ and 31–40‐year‐old groups. Furthermore, when combining the results of both the stepwise regression analysis and the HLA‐C*06:02 conditioning analysis, different variants were found to be independently associated with each psoriasis subgroup. Conclusions 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.