The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes.

The European Respiratory Journal
Tomoko NakanishiJ Brent Richards

Abstract

Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype in SERPINA1, is one of the most common inherited diseases. Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality. A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes. A polygenic risk score (PRS) for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.Among 458 164 European-ancestry participants in UK Biobank, 140 had the PI*ZZ genotype and only nine (6.4%, 95% CI 3.4-11.7%) of them were diagnosed with AATD. Those with PI*ZZ had a substantially higher odds of COPD (OR 8.8, 95% CI 5.8-13.3), asthma (OR 2.0, 95% CI 1.4-3.0), bronchiectasis (OR 7.3, 95%CI 3.2-16.8), pneumonia (OR 2.7, 95% CI 1.5-4.9) and cirrhosis (OR 7.8, 95% CI 2.5-24.6) diagnoses and a higher hazard of mortality (2.4, 95% CI 1.2-4.6), compared to PI*MM (w...Continue Reading

References

Jun 1, 1978·The Journal of Pediatrics·M L O'BrienW H Murphey
Jun 10, 1976·The New England Journal of Medicine·T Sveger
Dec 15, 1989·Annals of Internal Medicine·E K SilvermanE J Campbell
Mar 20, 1986·The New England Journal of Medicine·S ErikssonR Velez
Feb 1, 1995·American Journal of Respiratory and Critical Care Medicine·N Seersholm, A Kok-Jensen
Mar 5, 1999·The European Respiratory Journal·E Piitulainen, S Eriksson
Jul 5, 2005·The European Respiratory Journal·M DahlB G Nordestgaard
Oct 21, 2005·Chest·James K StollerCharlie Strange
Mar 29, 2007·Thorax·Dawn L DemeoEdwin K Silverman
Oct 22, 2008·Human Heredity·D L DeMeoE K Silverman
Jun 26, 2009·The New England Journal of Medicine·Edwin K Silverman, Robert A Sandhaus
Sep 10, 2010·Arthritis and Rheumatism·Alfred D MahrPeter A Merkel
Oct 1, 2011·American Journal of Respiratory and Critical Care Medicine·James K Stoller, Loutfi S Aboussouan
Jan 9, 2014·Trends in Endocrinology and Metabolism : TEM·Wieneke Dijk, Sander Kersten
Jan 17, 2014·American Journal of Respiratory and Critical Care Medicine·Kevin MolloyNoel G McElvaney
Sep 6, 2015·Therapeutic Advances in Respiratory Disease·Timm Greulich, Claus F Vogelmeier
Jan 8, 2016·Diabetes·Gian Paolo FadiniAngelo Avogaro
Feb 16, 2016·Nature Reviews. Genetics·William S BushDana C Crawford
Sep 17, 2017·Respiratory Research·Sebastian FähndrichUNKNOWN COSYCONET investigators
Dec 2, 2017·The European Respiratory Journal·Marc MiravitllesRobert A Stockley
Jan 31, 2018·COPD·Christopher L SandersFriedrich Kueppers
Dec 7, 2018·Nature Communications·Egil FerkingstadKari Stefansson
Mar 14, 2019·ERJ Open Research·Ildikó HorváthN Gerard McElvaney
Jul 22, 2019·The Lancet. Respiratory Medicine·Alessandro N FranciosiNoel G McElvaney

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Citations

Apr 2, 2021·The Application of Clinical Genetics·Susana Seixas, Patricia Isabel Marques
May 14, 2021·ERJ Open Research·Katherine A FawcettIan P Hall

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Methods Mentioned

BETA
genotyping

Software Mentioned

PheWAS

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