Abstract P185: Novel Loci for Blood Pressure Using Gene-alcohol Interactions and 1000g Imputed Data
Bibliographic record
Abstract
Alcohol consumption has a complex relationship with blood pressure (BP). Whereas heavy alcohol consumption is associated with high BP, moderate alcohol consumption is associated with unchanged or modestly lower BP. We performed genome-wide meta-analysis of single SNP x alcohol drinking status interaction on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) blood pressure using 1000G imputed data. Our preliminary results comprise 23 European ancestry studies, including 87,098 individuals with known drinking status. Interaction associations were preformed using linear regression with main and interaction effects and accounting for family structure as needed. Meta-analyses were performed with METAL, for a 2 degrees of freedom joint test, after applying study- and meta-based genomic control adjustments. Results were further filtered if the meta-analysis N < 5,000 individuals or if the number of cohorts contributing to meta-analysis were < 3 for each SNP. For DBP, six novel loci (TRAF3IP1, ANKRD36, NLGN1, UBE3D, OFCC1 and C1orf167) were identified (p < 5E-08). Known BP loci were found to be significant using the same interaction model, including MTHFR, CLCN6, NPPB, MECOM, NOS3, CACNB2, SH2B3, ATXN2, ALDH2, ATP2B1, CSK, FURIN and ZNF831. The significant DBP genes are enriched for hypertension (p-FDR=8.5E-08) and cardiac arrhythmias (p-FDR=5.3E-07) disease loci. MAP analyses identified similar loci as for DBP, while for SBP, ANKRD36 SNPs yielded the most significant associations. For PP, MYPN variants were most significant. In general for the joint test, known BP gene variants showed non-significant levels of meta-heterogeneity and common allele frequency (≥5%), whereas the novel loci often presented meta-heterogeneity and low allele frequency (≈1-5%). TRAF3IP1 interacts among others with TRAF3, reported in mice involved in a new pathway TRAF3-TBK1-AKT for cardiac hypertrophy and heart failure. ANKRD36 interacts with PHLPP2, involved in rats in FKBP51-PHLPP2-AKT signaling during cerebral ischemia/reperfusion injury. NLGN1 has been reported to associate with BP in ASCOT study (N=3,802), while in our meta-analysis out of 6 contributing studies, the joint test significance originates only from the GS_SFHS (N=6,504). Another significant result was C1orf167- rs12561919, a missense SNP considered cis-eQTL for neighboring BP known genes CLCN6 and MTHFR. Employing SNP x drinking status interaction for BP traits, we identified both novel and previously known BP genes. Our findings may provide insights into mechanisms underlying BP and inform lifestyle and therapeutic BP interventions.
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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 | 0.016 | 0.029 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.020 |
| Bibliometrics | 0.006 | 0.012 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.014 | 0.001 |
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".