title: Complex genetics of pulmonary diseases: lessons from genome-wide association studies and next-generation sequencing.
abstract: The advent of high-throughput technologies has provided exceptional assistance for lung scientists to discover novel genetic variants underlying the development and progression of complex lung diseases. However, the discovered variants thus far do not explain much of the estimated heritability of complex lung diseases. Here, we review the literature of successfully used genome-wide association studies (GWASs) and identified the polymorphisms that reproducibly underpin the susceptibility to various noncancerous complex lung diseases or affect therapeutic responses. We also discuss the inherent limitations of GWAS approaches and how the use of next-generation sequencing technologies has furthered our understanding about the genetic determinants of these diseases. Next, we describe the contribution of the metagenomics to understand the interactions of the airways microbiome with lung diseases. We then highlight the urgent need for new integrative genomics-phenomics methods to more effectively interrogate and understand multiple downstream "omics" (eg, chromatin modification patterns). Finally, we address the scarcity of genetic studies addressing under-represented populations such as African Americans and Hispanics.
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Ariz; Center for Biomedical Informatics and Biostatistics, University of Arizona, Tucson, Ariz; BIO5 Institute, University of Arizona, Tucson, Ariz.
authors.forename: Nima
authors.initials: N
authors.lastname: Pouladi
authors.affiliation: University of Arizona Health Sciences Center, University of Arizona, Tucson, Ariz; Arizona Respiratory Center, University of Arizona, Tucson, Ariz.
authors.forename: Christian
authors.initials: C
authors.lastname: Bime
authors.affiliation: University of Arizona Health Sciences Center, University of Arizona, Tucson, Ariz; Arizona Respiratory Center, University of Arizona, Tucson, Ariz.
authors.forename: Joe G N
authors.initials: JGN
authors.lastname: Garcia
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Ariz; Center for Biomedical Informatics and Biostatistics, University of Arizona, Tucson, Ariz; BIO5 Institute, University of Arizona, Tucson, Ariz; University of Arizona Health Sciences Center, University of Arizona, Tucson, Ariz; Institute for Genomics and Systems Biology, Argonne National Laboratory and University of Chicago, Chicago, Ill. Electronic address: yves@email.arizona.edu.
authors.forename: Yves A
authors.initials: YA
authors.lastname: Lussier
mesh_terms: D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008171:Lung Diseases / Q000235:genetics*; D017422:Sequence Analysis, DNA