Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Abstract

Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Ndufc2 Gene Inhibition Is Associated With Mitochondrial Dysfunction and Increased Stroke Susceptibility in an Animal Model of Complex Human Disease

“…Furthermore, NDUFC2 may represent a novel oncogene involved in breast cancer and intestinal adenocarcinoma, predicting poor prognosis 39, 40. Notably, the pathological relevance of NDUFC2/rs11237379 has been also highlighted through genome‐wide association studies in pulmonary disease 41, 42…”

Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation

“…Positively selected genes had a significantly higher ratio of nonsynonymous substitutions to synonymous substitutions than other genes in the high-altitude snub-nosed monkeys (P = 3.84 × 10 −3 for R. strykeri, 3.45 × 10 −6 for R. bieti, and 5.10 × 10 −8 for R. roxellana) (Supplementary Table 8). Further examination of these 16 genes found that 6 genes, including ARMC2, NT5DC1, RNASE4, CDT1, RTEL1, and DNAH11, have functional associations with lung function, angiogenesis, DNA repair, or respiratory cilia movement, suggesting a role in the high-altitude adaptation of the snub-nosed monkeys [19][20][21][22][23][24] (Table 1). Moreover, when the common substitutions for these six genes were examined in more mammalian species with publicly available genomes, no identical substitutions were found in those species (Supplementary Table 9 and Supplementary Note).…”

Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

“…Both LTL (11) and lung function (12,13) are known to be genetically regulated, and specific genes have been identified through genome-wide associations studies (14), but the known genes account for only a fraction of the heritable component estimated from family and twin data. Inter-individual variation in the amount and rate of decline with age both in lung function and in LTL has been less studied, although it is known to be affected by both genetic and environmental factors.…”