TY -的T1 - alpha - 1抗胰蛋白酶缺乏症”基因型相关的未确诊的疾病负担JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.01441 -2020欧元六世- 56 - 6 SP - 2001441 AU -录像,非盟- Forgetta, Vincenzo盟——手中,“非盟,平井伯昌Toyohiro盟——麋鹿,文森特AU -莱斯罗普,N2 - Alpha-1抗胰蛋白酶缺乏症(AATD)是最常见的遗传性疾病之一，主要由SERPINA1的PI*ZZ基因型引起。由于PI*ZZ与高疾病负担相关，并可通过戒烟部分预防，因此通过基因分型识别PI*ZZ个体可以改善健康结果。我们检测了来自英国生物库的PI*ZZ基因型在患有和未确诊AATD的个体中的频率，并评估了基因型与临床结果和死亡率的相关性。一项全现象关联研究(PheWAS)被用于揭示疾病与基因型的关联。采用1 s用力呼气量(FEV1)/用力肺活量(FVC)比值的多基因风险评分(PRS)来评估PI*ZZ的变量外显率。在英国生物银行的458 164名欧洲血统参与者中，有140人具有PI*ZZ基因型，其中只有9人(6.4%，95% CI 3.4-11.7%)被诊断为AATD。那些π* ZZ有更高的慢性阻塞性肺病的几率(或8.8,95%可信区间5.8 - -13.3),哮喘(或2.0,95%可信区间1.4 - -3.0),支气管扩张(或7.3,95%可信区间3.2 - -16.8),肺炎(或2.7,95%可信区间1.5 - -4.9)、肝硬化(-24.6或7.8,95% CI 2.5)诊断和更高的死亡率风险(2.4,95% CI 1.2 - -4.6),而π*毫米(野生型)424 (n = 398)。这些关联在吸烟者中更强。PheWAS与脓胸、气胸、恶病质、红细胞增多、动脉瘤和胰腺炎的发病几率增加有关。 Polygenic risk score and PI*ZZ were independently associated with FEV1/FVC <0.7 (OR 1.4 per 1-sd change, 95% CI 1.4–1.5 and OR 4.5, 95% CI 3.0–6.9, respectively).The important underdiagnosis of AATD, whose outcomes are partially preventable through smoking cession, could be improved through genotype-guided diagnosis.Only 6.4% of those with genotype-defined alpha-1 antitrypsin deficiency had been diagnosed with this serious disease in UK Biobank. Genotype-guided diagnosis could help to identify the thousands of people in the UK with this partially preventable disease. https://bit.ly/3dMu5Ng ER -