Complex genetics of pulmonary diseases: lessons from genome-wide association studies and next-generation sequencing.

TitleComplex genetics of pulmonary diseases: lessons from genome-wide association studies and next-generation sequencing.
Publication TypeJournal Article
Year of Publication2016
AuthorsPouladi N, Bime C, Garcia JGN, Lussier YA
JournalTransl Res
Volume168
Pagination22-39
Date Published2016 Feb
ISSN Number1878-1810
KeywordsGenetic Predisposition to Disease, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Lung Diseases, Sequence Analysis, DNA
Abstract

<p>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.</p>

DOI10.1016/j.trsl.2015.04.016
Alternate JournalTransl Res
PubMed ID26006746
PubMed Central IDPMC4658294
Grant ListK22 LM008308 / LM / NLM NIH HHS / United States
P30 CA023074 / CA / NCI NIH HHS / United States
R01 HL091889 / HL / NHLBI NIH HHS / United States
P30CA023074 / CA / NCI NIH HHS / United States