Dataset Information

Genetics of psoriasis: a basis for precision medicine.

ABSTRACT: Psoriasis is an inflammatory skin disease with a background of polygenic inheritance. Both environmental and genetic factors are involved in the etiology of the disease. In the last two decades, numerous studies have been conducted through linkage analysis, genome-wide association study (GWAS), and direct sequencing to explore the role of genetic variation in disease pathogenesis and progression. To date, >80 psoriasis susceptibility genes have been identified, including HLA-Cw6, IL12B, IL23R, and LCE3B/3C. Some genetic markers have been applied in disease prediction, clinical diagnosis, treatment, and new drug development, which could further explain the pathogenesis of psoriasis and promote the development of precision medicine. This review summarizes related research on genetic variation in psoriasis and explores implications of the findings in clinical application and the promotion of a personalized medicine project.

SUBMITTER: Ran D

PROVIDER: S-EPMC9026189 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Genetics of psoriasis: a basis for precision medicine.

Ran Delin D Cai Minglong M Zhang Xuejun X

Precision clinical medicine 20190624 2

Psoriasis is an inflammatory skin disease with a background of polygenic inheritance. Both environmental and genetic factors are involved in the etiology of the disease. In the last two decades, numerous studies have been conducted through linkage analysis, genome-wide association study (GWAS), and direct sequencing to explore the role of genetic variation in disease pathogenesis and progression. To date, >80 psoriasis susceptibility genes have been identified, including <i>HLA-Cw6</i>, <i>IL12B ...[more]

PMID: 35693758

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Project description:Kidney disease is a well-known health disparity in the United States where African Americans are affected at higher rates compared with other groups such as European Americans and Mexican Americans. Common genetic variants in the myosin, heavy chain 9, non-muscle (MYH9) gene were initially identified as associated with non-diabetic end-stage renal disease in African Americans, and it is now understood that these variants are in strong linkage disequilibrium with likely causal variants in neighboring APOL1. Subsequent genome-wide and candidate gene studies have suggested that MYH9 common variants among others are also associated with chronic kidney disease and quantitative measures of kidney function in various populations. In a precision medicine setting, it is important to consider genetic effects or genetic associations that differ across racial/ethnic groups in delivering data relevant to disease risk or individual-level patient assessment. Kidney disease and quantitative trait-associated genetic variants have yet to be systematically characterized in multiple racial/ethnic groups. Therefore, to further characterize the prevalence of these genetic variants and their association with kidney related traits, we have genotyped 10 kidney disease or quantitative trait-associated single nucleotide polymorphisms (SNPs) (rs2900976, rs10505955, rs10502868, rs1243400, rs9305354, rs12917707, rs17319721, rs2467853, rs2032487, and rs4821480) in 14,998 participants from the population-based cross-sectional National Health and Nutrition Examination Surveys (NHANES) III and 1999-2002 as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study. In this general adult population ascertained regardless of health status (6,293 non-Hispanic whites, 3,013 non-Hispanic blacks, and 3,542 Mexican Americans), we observed higher rates of chronic kidney disease among non-Hispanic blacks compared with the other groups as expected. We performed single SNP tests of association using linear regressions assuming an additive genetic model adjusted for age, sex, diastolic blood pressure, systolic blood pressure, and type 2 diabetes status for several outcomes including creatinine (urinary), creatinine (serum), albumin (urinary), eGFR, and albumin-to-urinary creatinine ratio (ACR). We also tested for associations between each SNP and chronic kidney disease and albuminuria using logistic regression. Surprisingly, none of the MYH9 variants tested was associated with kidney diseases or traits in non-Hispanic blacks (p>0.05), perhaps attributable to the clinical heterogeneity of kidney disease in this population. Several associations were observed in each racial/ethnic group at p<0.05, but none were consistently associated in the same direction in all three groups. The lack of significant and consistent associations is most likely due to power highlighting the importance of the availability of large, diverse populations for genetic association studies of complex diseases and traits to inform precision medicine efforts in diverse patient populations.

Dataset Information

Genetics of psoriasis: a basis for precision medicine.

Publications

Genetics of psoriasis: a basis for precision medicine.

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