Chronic Obstructive Pulmonary Disease Genetics: A Review of the Past and a Look Into the Future

Abstract

Abbreviations: single nucleotide polymorphism, SNP; genome-wide association studies, GWAS; forced expiratory volume in 1 second, FEV1; early-onset COPD, EOCOPD; National Emphysema Treatment Trial, NETT; Normative Aging Study, NAS; International COPD Genetics Network, ICGN; linkage disequilibrium, LD; Evaluation of COPD Longitudinally to Identify Surrogate Endpoints, ECLIPSE; cigarettes per day, CPD; forced volume capacity, FVC; Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium, CHARGE; messenger RNA, mRNA; body mass index, BMI; C-reactive protein, CRP; tumor necrosis factor-alpha, TNF-alpha; Clara cell secretory protein, CC16; surfactant protein D, SP-D; Funding: K12 HL120004, The Sheila J. Goodnight, MD, FCCP, Clinical Research Grant in Women's Lung Health, R01HL089856; P01HL105339; R01HL075478 Date of Acceptance: February 28, 2014 Citation: Hardin M, Silverman EK. Chronic obstructive pulmonary disease genetics: a review of the past and a look into the future.

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

“…Several studies have demonstrated the role of genetic factors in COPD development [179,180], with naturally occurring mutant murine models [165,181], conditional transgenic [182,183], and transgenic animals [184][185][186] developing emphysema. Murine models are favored over other animal models due to their large litter size and fast reproductive cycle, which speeds up the selection of favorable genetic traits that can be used in disease models [187].…”

Risk of Lung Disease in PI MZ Heterozygotes. Current Status and Future Research Directions

“…After the trials and tribulations of the candidate gene era in COPD genetics, the arrival of GWAS provided a welcome source of more consistent genetic association results for COPD (11). As noted above, to overcome the multiple statistical testing adjustments in GWAS, stringent levels of statistical significance (typically…”

Translating Lung Function Genome-Wide Association Study (GWAS) Findings

“…Many of these suffered from limited coverage of the genetic variation in target genes and small sample sizes thus limiting interpretation due to the lack of replication. These studies have been reviewed in detail elsewhere (Hardin M, 2014). Of note, a well powered study (8,300+ subjects) using a candidate gene approach identified association between SNPs in the matrix metalloprotease 12 gene (MMP12) and both FEV1 and COPD risk (Hunninghake et al, 2009).…”