PMID- 34656525 OWN - NLM STAT- MEDLINE DCOM- 20220309 LR - 20240205 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 161 IP - 2 DP - 2022 Feb TI - Prevalence of Alpha-1 Antitrypsin Deficiency, Self-Reported Behavior Change, and Health Care Engagement Among Direct-to-Consumer Recipients of a Personalized Genetic Risk Report. PG - 373-381 LID - S0012-3692(21)04099-X [pii] LID - 10.1016/j.chest.2021.09.041 [doi] AB - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition that predisposes to emphysema, cirrhosis, panniculitis, and vasculitis. Underrecognition has prompted efforts to enhance early detection and testing of at-risk individuals. Direct-to-consumer (DTC) genetic testing represents an additional method of detection. RESEARCH QUESTION: The study addressed three questions: (1) Does a DTC testing service identify previously undetected individuals with AATD? (2) What was the interval between initial AATD-related symptoms and initial diagnosis of AATD in such individuals? and (3) What was the behavioral impact of learning about a new diagnosis of AATD through a DTC test? STUDY DESIGN AND METHODS: In this cross-sectional study, 195,014 individuals responded to a survey within the 23andMe, Inc. research platform. RESULTS: Among 195,014 study participants, the allele frequency for the PI *S and PI *Z AATD variants was 21.6% (6.5% for PI *Z and 15.1% for PI *S); 0.63% were PI *ZZ, half of whom reported having a physician confirm the diagnosis. Approximately 27% of those with physician-diagnosed AATD reported first becoming aware of AATD through the DTC test. Among those newly aware participants, the diagnostic delay interval was 22.3 years. Participants frequently shared their DTC test results with health care providers (HCPs) and the reported impact of learning a diagnosis of AATD was high. For example, 51.1% of PI *ZZ individuals shared their DTC result with an HCP. The OR for PI *ZZ smokers to report smoking reduction as a result of receiving the DTC result was 1.7 (95% CI = 1.4-2.2) compared with those without a Z allele and for reduced alcohol consumption this was 4.0 (95% CI = 2.6-5.9). INTERPRETATION: In this largest available report on DTC testing for AATD, this test, in combination with clinical follow-up, can help to identify previously undiagnosed AATD patients. Moreover, receipt of the DTC AATD report was associated with positive behavior change, especially among those with risk variants. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Ashenhurst, James R AU - Ashenhurst JR AD - 23andMe Inc., Sunnyvale, CA. Electronic address: jashenhurst@23andme.com. FAU - Nhan, Hoang AU - Nhan H AD - 23andMe Inc., Sunnyvale, CA. FAU - Shelton, Janie F AU - Shelton JF AD - 23andMe Inc., Sunnyvale, CA. FAU - Wu, Shirley AU - Wu S AD - 23andMe Inc., Sunnyvale, CA. FAU - Tung, Joyce Y AU - Tung JY AD - 23andMe Inc., Sunnyvale, CA. FAU - Elson, Sarah L AU - Elson SL AD - 23andMe Inc., Sunnyvale, CA. FAU - Stoller, James K AU - Stoller JK AD - Education Institute and Respiratory Institute, Cleveland Clinic, Cleveland, OH. CN - 23andMe Research Team AD - 23andMe Inc., Sunnyvale, CA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211014 PL - United States TA - Chest JT - Chest JID - 0231335 SB - IM CIN - Chest. 2023 Apr;163(4):e197. PMID: 37031997 CIN - Chest. 2023 Apr;163(4):e198. PMID: 37031998 CIN - MMW Fortschr Med. 2023 Dec;165(21-22):36-37. PMID: 38064074 MH - *Direct-To-Consumer Screening and Testing MH - Female MH - *Genetic Testing MH - Genotype MH - Humans MH - Male MH - Middle Aged MH - Prevalence MH - *Self Report MH - alpha 1-Antitrypsin Deficiency/*epidemiology/*genetics OTO - NOTNLM OT - AATD OT - SERPINA1 OT - alpha-1 antitrypsin deficiency OT - consumer genomics OT - direct-to-consumer OT - lung disease OT - rare disease FIR - Agee, Michelle IR - Agee M FIR - Aslibekyan, Stella IR - Aslibekyan S FIR - Auton, Adam IR - Auton A FIR - Babalola, Elizabeth IR - Babalola E FIR - Bell, Robert K IR - Bell RK FIR - Bielenberg, Jessica IR - Bielenberg J FIR - Bryc, Katarzyna IR - Bryc K FIR - Bullis, Emily IR - Bullis E FIR - Cameron, Briana IR - Cameron B FIR - Coker, Daniella IR - Coker D FIR - Partida, Gabriel Cuellar IR - Partida GC FIR - Dhamija, Devika IR - Dhamija D FIR - Das, Sayantan IR - Das S FIR - Elson, Sarah L IR - Elson SL FIR - Filshtein, Teresa IR - Filshtein T FIR - Fletez-Brant, Kipper IR - Fletez-Brant K FIR - Fontanillas, Pierre IR - Fontanillas P FIR - Freyman, Will IR - Freyman W FIR - Gandhi, Pooja M IR - Gandhi PM FIR - Heilbron, Karl IR - Heilbron K FIR - Hicks, Barry IR - Hicks B FIR - Hinds, David A IR - Hinds DA FIR - Huber, Karen E IR - Huber KE FIR - Jewett, Ethan M IR - Jewett EM FIR - Jiang, Yunxuan IR - Jiang Y FIR - Kleinman, Aaron IR - Kleinman A FIR - Kukar, Katelyn IR - Kukar K FIR - Lane, Vanessa A IR - Lane VA FIR - Lin, Keng-Han IR - Lin KH FIR - Lowe, Maya IR - Lowe M FIR - Luff, Marie K IR - Luff MK FIR - McCreight, Jennifer C IR - McCreight JC FIR - McIntyre, Matthew H IR - McIntyre MH FIR - McManus, Kimberly F IR - McManus KF FIR - Micheletti, Steven J IR - Micheletti SJ FIR - Moreno, Meghan E IR - Moreno ME FIR - Mountain, Joanna L IR - Mountain JL FIR - Mozaffari, Sahar V IR - Mozaffari SV FIR - Nandakumar, Priyanka IR - Nandakumar P FIR - Noblin, Elizabeth S IR - Noblin ES FIR - O'Connell, Jared IR - O'Connell J FIR - Petrakovitz, Aaron A IR - Petrakovitz AA FIR - Poznik, G David IR - Poznik GD FIR - Schumacher, Morgan IR - Schumacher M FIR - Shastri, Anjali J IR - Shastri AJ FIR - Shelton, Janie F IR - Shelton JF FIR - Shi, Jingchunzi IR - Shi J FIR - Shringarpure, Suyash IR - Shringarpure S FIR - Tian, Chao IR - Tian C FIR - Tran, Vinh IR - Tran V FIR - Tung, Joyce Y IR - Tung JY FIR - Wang, Xin IR - Wang X FIR - Wang, Wei IR - Wang W FIR - Weldon, Catherine H IR - Weldon CH FIR - Wilton, Peter IR - Wilton P EDAT- 2021/10/18 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/10/17 20:36 PHST- 2021/03/23 00:00 [received] PHST- 2021/09/09 00:00 [revised] PHST- 2021/09/12 00:00 [accepted] PHST- 2021/10/18 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/10/17 20:36 [entrez] AID - S0012-3692(21)04099-X [pii] AID - 10.1016/j.chest.2021.09.041 [doi] PST - ppublish SO - Chest. 2022 Feb;161(2):373-381. doi: 10.1016/j.chest.2021.09.041. Epub 2021 Oct 14.