Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia.

Ho-Young Son,Hyouk-Soo Kwon,Jong-Il Kim,Kyung-Up Min,Mi Kyeong Lee,Joohon Sung,Hyun-Jin Kim,Sun-Hwa Im,Seong-Wook Sohn,Hyung-Lae Kim,Bayasgalan Gombojav,Jeong-Sun Seo,Daniel S Park,Andrew Dewan

doi:10.1371/journal.pone.0139716

Abstract

The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

Highlights

Pulmonary function, which is commonly measured by spirometry, is a good index of the physiological condition of the lung and airways [1]
We found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study
Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia

Summary

Introduction

Pulmonary function, which is commonly measured by spirometry, is a good index of the physiological condition of the lung and airways [1]. Studies have reported COPD aggregation and significant heritability of spirometry-measured pulmonary function [1, 6, 7]. To discover genetic loci related with pulmonary function and COPD, several linkage studies have been conducted using the quantitative spirometry measures FEV1, FVC, and the FEV1/ FVC ratio [8, 9]. Genome-wide association studies (GWAS) have revealed various genes showing significant associations with pulmonary function [12, 13]. Numerous genome-wide linkage and association studies have revealed a number of genes and genetic loci associated with pulmonary function, these genetic results explain only a small proportion of the genetic variation needed to estimate the heritability and variance of the trait [17]. Most previous association studies on pulmonary function have focused on populations of European ancestry and not on those of Asian ancestry

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