Journal Article

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population

Liao, Wen-Ling, Liu, Ting-Yuan, Lin, Wei-De, Tsai, Fuu-Jen, Chen, Wei-Cheng, Chen, Yu-Chia

2024

Overview

Background Chronic Obstructive Pulmonary Disease (COPD) describes a group of progressive lung diseases causing breathing difficulties. While COPD development typically involves a complex interplay between genetic and environmental factors, genetics play a role in disease susceptibility. This study used genome-wide association studies (GWAS) and polygenic risk score (PRS) to elucidate the genetic basis for COPD in Taiwanese patients. Results GWAS was performed on a Taiwanese COPD case–control cohort with a sample size of 5,442 cases and 17,681 controls. Additionally, the PRS was calculated and assessed in our target groups. GWAS results indicate that although there were no single nucleotide polymorphisms (SNPs) of genome-wide significance, prominent COPD susceptibility loci on or nearby genes such as WWTR1 , EXT1 , INTU , MAP3K7CL , MAMDC2 , BZW1/CLK1 , LINC01197 , LINC01894 , and CFAP95 ( C9orf135 ) were identified, which had not been reported in previous studies. Thirteen susceptibility loci, such as CHRNA4 , AFAP1 , and DTWD1 , previously reported in other populations were replicated and confirmed to be associated with COPD in Taiwanese populations. The PRS was determined in the target groups using the summary statistics from our base group, yielding an effective association with COPD (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02–1.17, p  = 0.011). Furthermore, replication a previous lung function trait PRS model in our target group, showed a significant association of COPD susceptibility with PRS of Forced Expiratory Volume in one second (FEV 1 )/Forced Vital Capacity (FCV) (OR 0.89, 95% CI 0.83–0.95, p  = 0.001). Conclusions Novel COPD-related genes were identified in the studied Taiwanese population. The PRS model, based on COPD or lung function traits, enables disease risk estimation and enhances prediction before suffering. These results offer new perspectives on the genetics of COPD and serve as a basis for future research.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Airway management / Analysis / Animal Genetics and Genomics / Asian People - genetics / Biobanks / Biomedical and Life Sciences / Care and treatment / Case-Control Studies / Chronic obstructive pulmonary disease / Confidence intervals / Consortia / Development and progression / Diagnosis / Disease prevention / Disease susceptibility / Emphysema / Environmental factors / Female / Genes / Genetic aspects / Genetic association / Genetic Biobank of China Medical University Hospital / Genetic Loci / Genetic Predisposition to Disease / Genetic Risk Score / Genetics / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genomics / Growth factors / Health aspects / Health risk assessment / Health risks / Humans / Inflammation / Life Sciences / Lung diseases / Lung diseases, Obstructive / Lungs / Male / Medical records / Medical research / Medicine, Experimental / Microarrays / Microbial Genetics and Genomics / Middle Aged / Missing data / Multifactorial Inheritance / Nucleotides / Plant Genetics and Genomics / Polygenic inheritance / Polygenic risk score / Polymorphism, Single Nucleotide / Population genetics / Population studies / Populations / Precision medicine / Proteomics / Pulmonary Disease, Chronic Obstructive - genetics / Quality control / Research ethics / Respiratory function / Risk / Risk Factors / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Smoking / Surfactants / Susceptibility / Taiwan / Taiwanese population / Target groups