Article Figures & Data
- Figure 1
Identification and selection of pathogenic/likely pathogenic variants in the CNSR-III cohort. In total, 88 604 observed variants in 181 genes were enrolled in this study. We used 345 pathogenic/likely pathogenic variants after filtering using the ClinVar database (left), and 776 novel pathogenic/likely pathogenic variants after annotation using the ACMG/AMP guidelines (right). ACMG, American College of Medical Genetics and Genomics; AMP, Association for Molecular Pathology; CNSR-III, the Third China National Stroke Registry; LB, likely benign.
- Figure 2
Individuals diagnosed and potentially missed diagnoses. Flow chart (left) illustrating the number of individuals harbouring one or more P/LP variant, and the number of individuals predicted to develop one or more monogenic disease. Bar plot (right) illustrating the proportions of the groups at risk for one monogenic disease, showing their likelihood of a missed diagnosis. EHR, electronic health record; P/LP, pathogenic or likely pathogenic.
- Figure 3
Genetic architecture of stroke. Each gene related to monogenic stroke identified in 759 individuals was classified into five subgroups: large-artery disease, small-vessel disease, embolic stroke, a prothrombotic state and other diseases (shown in the middle text circle). The proportions of affected genes are shown in the outermost circle.
- Figure 4
Characteristics of 227 individuals diagnosed with Mendelian causes of stroke. The bars represent the number of individuals diagnosed with Mendelian causes of stroke identified for each gene, which are coloured according to the classification of stroke aetiology. Three individuals with two monogenic diseases were ruled out. The percentages in the boxes indicate the distribution of risk factors, including hypertension, hyperlipidaemia, diabetes, coronary heart disease, atrial fibrillation, smoking history, drinking history and body mass index ≥25.
- Table 1
Characteristics of the included patients in CNSR-III
NGS analysis cohort (n=10 428) CNSR-III cohort (n=15 166) Remaining cohort (n=4738) Age at time of study entry，mean±SD 62.25±11.32 62.23±11.30 62.19±11.26 ≤45 years 735 (7.05) 1074 (7.08) 339 (7.15) >45 years 9693 (92.95) 14 092 (92.92) 4399 (92.85) Male, n (%) 7137 (68.44) 10 364 (68.34) 3277 (68.11) Ethnicity, Han, n (%) 10 118 (97.03) 14 726 (97.10) 4608 (97.26) Current smoker, n (%) 3320 (31.84) 4752 (31.33) 1432 (30.22) Heavy drinker, n (%) 1482 (14.21) 2126 (14.02) 644 (13.59) BMI (≥25 kg/m²) 4464 (42.81) 6468 (42.65) 2004 (42.30) Medical history, n (%) Ischaemic stroke 2349 (22.53) 3355 (22.12) 1006 (21.23) Coronary heart diseases 1152 (11.05) 1608 (10.60) 456 (9.62) Atrial fibrillation 737 (7.07) 1019 (6.72) 282 (5.95) Hypertension 6540 (62.72) 9494 (62.60) 2954 (62.35) Diabetes mellitus 2490 (23.88) 3510 (23.14) 1020 (21.53) Dyslipidaemia 882 (8.46) 1191 (7.85) 309 (6.52) Stroke type IS 9728(93.3) 14 146 (93.27) 4418 (93.25) TIA 700 (6.7) 1020 (6.73) 320 (6.75) Family history of Stroke 1395 (13.38) 2013 (13.27) 618 (13.04) CCS Large artery atherosclerosis 2999 (28.76) 4364 (28.77) 1365 (28.81) Cardioaortic embolism 718 (6.89) 971 (6.40) 253 (5.34) Small arterial occlusion 2614 (25.07) 3747 (24.71) 1133 (23.91) Other aetiologies 86 (0.82) 152 (1.00) 66 (1.39) Undetermined aetiology 4011 (38.46) 5932 (39.11) 1921 (40.54) Note: Heavy drinker: alcohol ≥20 g/day.
BMI, body mass index; CCS, Causative Classification System for Ischaemic Stroke; CNSR-III, the Third China National Stroke Registry; IS, ischaemic stroke; NGS, next-generation sequencing; TIA, transient ischaemic attack.
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