- FIGURE 1
Traits associated with the SERPINA1 Z allele in UK Biobank. Traits displayed are those with a false discovery rate (FDR) <0.01 from phenome-wide association study of 2411 phenotypes across 379 101 UK Biobank participants using the a) heterozygous model for the Z allele (wild-type versus heterozygous individuals) and b) recessive model for the Z allele (wild-type and heterozygous individuals versus individuals homozygous for the Z allele). HES: hospital episode statistics; FBC: full blood count; FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; PEF: peak expiratory flow; ENT: ear, nose and throat.
- TABLE 1
Association between the SERPINA1 Z allele and blood biomarkers in unrelated, European UK Biobank participants
Biomarker Heterozygous genetic model Recessive genetic model β±se p-value β±se p-value Alanine aminotransferase U·L−1 1.163±0.112 2.95×10−25 3.037±1.246 0.015 Albumin g·L−1 0.712±0.022 3.11×10−229 0.306±0.243 0.208 Alkaline phosphatase U·L−1 2.968±0.213 5.81×10−44 2.379±2.373 0.316 Apolipoprotein B g·L−1 −0.0037±0.0021 0.082 0.042±0.024 0.086 Apolipoprotein A g·L−1 −0.0045±0.0019 0.020 0.019±0.022 0.375 Aspartate aminotransferase U·L−1 0.707±0.086 2.27×10−16 6.353±0.956 3.04×10−11 C-reactive protein mg·L−1 −0.174±0.036 1.11×10−6 0.192±0.396 0.628 Calcium mmol·L−1 0.012±0.00080 4.01×10−50 0.01±0.009 0.265 Cholesterol mmol·L−1 0.0051±0.0092 0.576 0.19±0.102 0.063 Creatinine μmol·L−1 −0.067±0.129 0.601 −0.94±1.435 0.512 Cystatin C mg·L−1 0.0090±0.0013 8.91×10−12 0.019±0.015 0.204 Direct bilirubin μmol·L−1 0.041±0.0073 1.64×10−8 0.158±0.079 0.046 eGFR# −0.241±0.157 0.125 −1.810±1.732 0.296 γ-Glutamyltransferase U·L−1 0.253±0.342 0.460 8.045±3.818 0.035 Glucose mmol·L−1 −0.0032±0.010 0.758 −0.133±0.114 0.244 HbA1c mmol·mol−1 −0.187±0.052 3.40×10−4 −1.781±0.588 2.46×10−3 HDL–cholesterol mmol·L−1 0.0015±0.0030 0.605 0.142±0.033 2.01×10−5 IGF-1 nmol·L−1 −0.212±0.045 2.35×10−6 −2.245±0.5 7.19×10−6 LDL direct mmol·L−1 0.011±0.007 0.113 0.115±0.079 0.145 Lipoprotein A nmol·L−1 −0.324±0.452 0.474 −0.151±5.115 0.976 Oestradiol pmol·L−1 9.577±8.441 0.257 88.051±96.144 0.360 Phosphate mmol·L−1 0.0027±0.0013 0.042 −0.014±0.015 0.352 Rheumatoid factor IU·mL−1 0.113±0.529 0.832 −3.27±5.7 0.566 SHBG nmol·L−1 4.531±0.218 1.06×10−95 40.573±2.402 5.33×10−64 Testosterone nmol·L−1 0.37±0.023 1.84×10−57 2.986±0.258 6.96×10−31 Total bilirubin μmol·L−1 0.146±0.035 3.54×10−5 0.52±0.391 0.184 Total protein g·L−1 0.578±0.035 1.06×10−62 0.459±0.382 0.229 Triglycerides mmol·L−1 −0.023±0.0082 4.69×10−3 −0.324±0.092 4.21×10−4 Urate μmol·L−1 1.096±0.56 0.050 −1.325±6.252 0.832 Urea mmol·L−1 0.051±0.011 2.69×10−6 0.06±0.122 0.620 Vitamin D nmol·L−1 −0.041±0.175 0.816 −2.547±1.955 0.193 Results are based on linear regression adjusting for sex, age, age2, ancestry-based principal components and genotyping array. The heterozygous or recessive genetic model was also included in the regression as shown. eGFR: estimated glomerular filtration rate; HbA1c: glycated haemoglobin; HDL: high-density lipoprotein; IGF: insulin-like growth factor; LDL: low-density lipoprotein; SHBG: sex hormone-binding globulin. #: calculated using the following formula: if cystatin C (cys)≤0.8, then eGFR=133*((cys/0.8)**−0.499)*(0.996**age)*[0.932 if female]; whereas if cys>0.8, then eGFR=133*((cys/0.8)**−1.328)*(0.996**age)*[0.932 if female].
- TABLE 2
Association between the SERPINA1 Z allele and height, lung function traits, and COPD in unrelated, European UK Biobank participants
Genetic model Smoking status Test/comparison n Height cm FEV1 mL FEV1/FVC FVC mL COPD# COPD GOLD 1–4¶ β±se p-value β±se p-value β±se p-value β±se p-value OR (95% CI) p-value OR (95% CI) p-value Het All 11 877/291 383 1.023±0.059 3.91×10−68 9.26±4.53 0.041 0.00091±0.00057 0.108 9.38±5.43 0.084 1.05 (0.96–1.14) 0.268 1.04 (0.98–1.09) 0.171 Ever-smokers 5357/133 779 1.027±0.087 8.53×10−32 −2.63±7.05 0.709 −0.0017±0.00091 0.062 5.47±8.28 0.509 1.16 (1.05–1.29) 0.005 1.12 (1.04–1.20) 0.001 Never-smokers 6520/157 604 1.022±0.079 3.03×10−38 19.36±5.84 9.21×10−4 0.0031±0.00071 1.22×10−5 12.77±7.15 0.074 0.87 (0.75–1.01) 0.070 0.93 (0.86–1.02) 0.113 Rec All 93/303 260 1.644±0.650 0.011 −249.21±50.22 6.96×10−7 −0.051±0.0063 3.54×10−16 −132.16±60.09 0.028 7.42 (4.29–12.27) 5.67×10−14 4.58 (2.93–7.05) 8.67×10−12 Ever-smokers 35/139 136 1.242±1.062 0.242 −379.21±85.54 9.30×10−6 −0.081±0.011 2.00×10−13 −177.95±100.35 0.076 9.19 (4.19–19.00) 6.27×10−9 6.13 (3.07–12.29) 2.30×10−7 Never-smokers 58/164 124 1.873±0.821 0.023 −174.68±60.68 0.004 −0.034±0.0074 4.95×10−6 −107.69±74.23 0.147 5.98 (2.66–12.03) 2.69×10−6 3.68 (2.01–6.47) 1.11×10−5 Results are based on linear (or logistic, in the case of COPD) regression adjusting for sex, age, age2, ancestry-based principal components, genotyping array and, in the case of lung function and COPD, standing height. The heterozygote (Het) or recessive (Rec) genetic model was also included in the regression as shown. FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease. #: spirometrically defined as FEV1/FVC <0.7 and FEV1<80% predicted; ¶: defined as FEV1/FVC <0.7.
Supplementary Materials
Supplementary Material
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Supplementary material 00049-2021.SUPPLEMENT
Table S1 00049-2021.TableS1
Table S2 00049-2021.TableS2
Table S3 00049-2021.TableS3
Table S4 00049-2021.TableS4
Table S5 00049-2021.TableS5
Table S6 00049-2021.TableS6
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