Genome‐Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores
Bibliographic record
Abstract
Background Electrocardiography is one of the most valuable noninvasive diagnostic tools in determining the presence of many cardiovascular diseases. Genetic factors are important in determining ECG abnormalities and their link to cardiovascular diseases. Genome‐wide association studies and polygenic risk scores (PRSs) have been conducted for various ECG traits such as QT interval and QRS duration. However, these studies mainly focused on cohorts of European descent. Methods In this cohort study, genome‐wide association studies for 6 ECG traits (RR, PR, corrected QT interval [QTc], QRS, JT, and P wave duration) were conducted in a Middle Eastern cohort from the Qatar Precision Health Institute, comprising 13 827 subjects with whole‐genome sequence data. Middle Eastern PRSs were developed using clumping and thresholding, and their performance was compared with 26 published PRSs. Genetic predisposition to long QT syndrome was explored using rare variant analysis. Results Seventy‐four independent loci were obtained with genome‐wide significance across the 6 traits ( P <5×10 −8 ). Of the 74 loci, 67 (90.5%) were previously reported, and 7 loci (9.5%) were novel and contained 6 genes: STAC and CSMD1 for PR, ANK1 and NCOA2 for QRS, LSP1 for QTc, and MKLN1 for P wave duration. All 26 published PRSs showed good performance in our cohort. PGS002276 showed the best performance for QTc ( R 2 =0.059, P =4.83×10 −185 ), PGS002166 showed the best performance for QRS ( R 2 =0.024, P =1.53×10 −75 ), and PGS000905 showed the best performance for PR ( R 2 =0.053, P =2.57×10 −165 ). Some of these PRSs were associated with cardiovascular diseases. For example, PGS003500, a QTc PRS, was significantly associated with cardiomyopathy (odds ratio per 1 SD=1.58 [95% CI, 1.23–2.01]; P =2.42×10 −4 ). Middle Eastern PRSs substantially outperformed published PRSs and did not perform well in the UK Biobank data. Ten pathogenic variants, including 3 that are specific to Qatari individuals, were observed in 17 long QT syndrome genes and were carried by 19 individuals. The QTc average was larger for mutation carriers (415.6±23.5 versus 402.3±18.5 in noncarriers). Five‐year follow‐up data did not show a significant change in ECG patterns, regardless of mutation status and PRS values. Four of 2302 individuals had prolonged QTc intervals over the 2 time points. Conclusions In this first genome‐wide association study for ECG traits in the Middle East using whole‐genome sequence data, 7 novel loci (6 genes) were identified. Published PRSs performed well, but newly developed Middle Eastern–specific PRSs performed the best. Novel variants in long QT syndrome genes were observed for the first time in Qatari individuals. Follow‐up data did not show significant changes in ECG patterns.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".