Genetics of Complex Respiratory Diseases: Implications for Pathophysiology and Pharmacology Studies

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2011 Jan 15

PMID 21232051

Citations 6

Authors

Maen Obeidat

Ian P Hall

Affiliations

Soon will be listed here.

Abstract

There has been a huge influx of data on the genetics and genomics of respiratory diseases in the last few years. Powered by large sample sizes from collaborations worldwide, recent genome-wide association studies have convincingly implicated variants in different regions in the genome for association with complex respiratory traits. These new associations have the potential to offer invaluable insight into the pathophysiology of the normal and diseased respiratory system. The functional mechanisms underlying effects of both identified and novel variants will be the focus of research over the next few years. The identification of these mechanisms will not only increase our understanding of disease but may allow the development of new therapies to alleviate respiratory conditions. The implications of these approaches for studies of asthma and Chronic Obstructive Pulmonary Disease are covered in this review.

Citing Articles

Precision medicine for respiratory diseases: A current viewpoint.

Georgakopoulou V, Lempesis I, Sklapani P, Trakas N, Spandidos D Med Int (Lond). 2024; 4(4):31.

PMID: 38680944 PMC: 11046260. DOI: 10.3892/mi.2024.155.

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Guillen-Guio B, Paynton M, Allen R, Chin D, Donoghue L, Stockwell A ERJ Open Res. 2024; 10(1).

PMID: 38375425 PMC: 10875457. DOI: 10.1183/23120541.00553-2023.

Genetic epidemiology and Mendelian randomization for informing disease therapeutics: Conceptual and methodological challenges.

Paternoster L, Tilling K, Davey Smith G PLoS Genet. 2017; 13(10):e1006944.

PMID: 28981501 PMC: 5628782. DOI: 10.1371/journal.pgen.1006944.

Association of interleukin 7 receptor (rs1494555 and rs6897932) gene polymorphisms with asthma in a north Indian population.

Sinha S, Singh J, Jindal S Allergy Rhinol (Providence). 2015; 6(3):168-76.

PMID: 26686208 PMC: 5391485. DOI: 10.2500/ar.2015.6.0137.

Novel cAMP signalling paradigms: therapeutic implications for airway disease.

Billington C, Hall I Br J Pharmacol. 2011; 166(2):401-10.

PMID: 22013890 PMC: 3417475. DOI: 10.1111/j.1476-5381.2011.01719.x.

References

Mathias R, Grant A, Rafaels N, Hand T, Gao L, Vergara C . A genome-wide association study on African-ancestry populations for asthma. J Allergy Clin Immunol. 2009; 125(2):336-346.e4. PMC: 3606015. DOI: 10.1016/j.jaci.2009.08.031. View

Mardis E . The impact of next-generation sequencing technology on genetics. Trends Genet. 2008; 24(3):133-41. DOI: 10.1016/j.tig.2007.12.007. View

Zhang Y, Leaves N, Anderson G, Ponting C, Broxholme J, Holt R . Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet. 2003; 34(2):181-6. DOI: 10.1038/ng1166. View

Weiss S, Raby B, Rogers A . Asthma genetics and genomics 2009. Curr Opin Genet Dev. 2009; 19(3):279-82. DOI: 10.1016/j.gde.2009.05.001. View

Noguchi E, Yokouchi Y, Zhang J, Shibuya K, Shibuya A, Bannai M . Positional identification of an asthma susceptibility gene on human chromosome 5q33. Am J Respir Crit Care Med. 2005; 172(2):183-8. DOI: 10.1164/rccm.200409-1223OC. View

Hubert H, Fabsitz R, Feinleib M, Gwinn C . Genetic and environmental influences on pulmonary function in adult twins. Am Rev Respir Dis. 1982; 125(4):409-15. DOI: 10.1164/arrd.1982.125.4.409. View

Manolio T, Collins F, Cox N, Goldstein D, Hindorff L, Hunter D . Finding the missing heritability of complex diseases. Nature. 2009; 461(7265):747-53. PMC: 2831613. DOI: 10.1038/nature08494. View

Balaci L, Spada M, Olla N, Sole G, Loddo L, Anedda F . IRAK-M is involved in the pathogenesis of early-onset persistent asthma. Am J Hum Genet. 2007; 80(6):1103-14. PMC: 1867098. DOI: 10.1086/518259. View

Duffy D, Martin N, Battistutta D, Hopper J, Mathews J . Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis. 1990; 142(6 Pt 1):1351-8. DOI: 10.1164/ajrccm/142.6_Pt_1.1351. View

10.

Tavendale R, Macgregor D, Mukhopadhyay S, Palmer C . A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J Allergy Clin Immunol. 2008; 121(4):860-3. DOI: 10.1016/j.jaci.2008.01.015. View

11.

Allen M, Heinzmann A, Noguchi E, Abecasis G, Broxholme J, Ponting C . Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nat Genet. 2003; 35(3):258-63. DOI: 10.1038/ng1256. View

12.

Barton S, Koppelman G, Vonk J, Browning C, Nolte I, Stewart C . PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. J Allergy Clin Immunol. 2009; 123(6):1391-400.e17. DOI: 10.1016/j.jaci.2009.03.014. View

13.

Pillai S, Ge D, Zhu G, Kong X, Shianna K, Need A . A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009; 5(3):e1000421. PMC: 2650282. DOI: 10.1371/journal.pgen.1000421. View

14.

Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T . Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008; 40(5):638-45. PMC: 2672416. DOI: 10.1038/ng.120. View

15.

McClearn G, Svartengren M, Pedersen N, HELLER D, Plomin R . Genetic and environmental influences on pulmonary function in aging Swedish twins. J Gerontol. 1994; 49(6):264-8. DOI: 10.1093/geronj/49.6.m264. View

16.

Metzker M . Sequencing technologies - the next generation. Nat Rev Genet. 2009; 11(1):31-46. DOI: 10.1038/nrg2626. View

17.

Risch N . Searching for genetic determinants in the new millennium. Nature. 2000; 405(6788):847-56. DOI: 10.1038/35015718. View

18.

Bisgaard H, Bonnelykke K, Sleiman P, Brasholt M, Chawes B, Kreiner-Moller E . Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood. Am J Respir Crit Care Med. 2008; 179(3):179-85. DOI: 10.1164/rccm.200809-1436OC. View

19.

Altshuler D, Daly M, Lander E . Genetic mapping in human disease. Science. 2008; 322(5903):881-8. PMC: 2694957. DOI: 10.1126/science.1156409. View

20.

Ober C, Butte A, Elias J, Lusis A, Gan W, Banks-Schlegel S . Getting from genes to function in lung disease: a National Heart, Lung, and Blood Institute workshop report. Am J Respir Crit Care Med. 2010; 182(6):732-7. PMC: 2949401. DOI: 10.1164/rccm.201002-0180PP. View