Lung function can be measured in terms of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC); the total amount that can be exhaled after maximum inhale, as well as the ratio between the two. Genetic elements associated with lung function are also correlated with risk of pulmonary disease, however due to the phenomenon of missing heritability these associations do not fully explain the genetic influence on lung function.
Woo Jin Kim of Kangwon National University School of Medicine, South Korea, led a genome wide association study (GWAS) using exome-based genotyping array on 7,524 individuals from the Korean Genome and Epidemiology Study (KoGES), which consists of six prospective cohorts, to gain further insight into genetic influence on lung function. The results were published in the Korean Journal of Internal Medicine.
Coding variants in the small integral membrane protein 29 (SMIM29) and the High Mobility Group AT-Hook 1 (HMGA1) locus on chromosome 6p21, the ARF GTPase-activating protein (GIT2) locus on chromosome 12q24, and the Rho Guanine Nucleotide Exchange Factor 40 (ARHGEF40) locus on chromosome 14q11 were identified as having a significant association with FEV1.
A previously reported association between lung function and chronic obstructive pulmonary disease (COPD) was confirmed, which consisted of Family With Sequence Similarity 13 Member A (FAM13A) locus on chromosome 4q22, Tenascin XB (TNXB), and the advanced glycation endproducts receptor (AGER) locus on chromosome 6p21.
The mechanism of these associations were not addressed in this study. Most of the genome is non-coding, but this study only used exome coding data. The study did not uncover the source of the missing heritability of lung function, potentially due to the aforementioned reason.
“In conclusion, we have newly identified a common coding variant in or near SMIM29 (C6orf1), HMGA1, and one missense low-frequency variant in ARHGEF40, that are associated with lung function. Although a large sample size may be required to strengthen our results, we present additional evidence to support the notion that the genetic contribution to lung function includes polygenic architecture with low-frequency and common genetic variants in the Korean population,” stated the authors.