Obesity- and Lipid-Related Traits May Causally Contribute to Sepsis-Associated Acute Kidney Injury
Bibliographic record
Abstract
OBJECTIVES: Acute kidney injury (AKI) is a major complication of sepsis resulting in substantial morbidity and mortality. We used genome-wide association study (GWAS) data together with Mendelian randomization (MR) analysis in multiple cohorts of different ancestries to identify traits potentially contributing to sepsis-associated AKI (Septic-AKI). DESIGN: Natural experiment and case-control study. SETTING: ICU patients, FinnGen ( finngen.fi ), and U.K. Biobank participants. PATIENTS: Adults with sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a discovery GWAS in the U.K. Biobank by selecting, after quality control, 4584 European Septic-AKI patients as cases, and 7090 European sepsis patients without AKI as controls. Causal inference analyses using two sample MR combined these GWAS results with Integrative Epidemiology Unit Open Genome-Wide Association Studies results for 118 clinical risk factors and 386 metabolites and, separately, for 13 lipid classes from FinnGen GWAS results. We tested for replication of positive findings in two independent genotyped septic shock cohorts (Vasopressin and Septic Shock Trial [VASST] cohort n = 632 and Japanese Septic Shock Cohort [Chiba] cohort n = 536). Variants in the GALNTL6 gene were associated with Septic-AKI (rs149773593; odds ratio = 2.18; p = 3.0 × 10 -8 ) in U.K. Biobank patients. GALNTL6 is associated with cardiometabolic traits, which we then focused on. Increased body mass index was associated with increased serum creatinine in both septic shock cohorts ( p < 0.0001). Obesity and metabolic traits, most frequently related to very low-density lipoprotein, were identified as potentially causal contributors to Septic-AKI. Combining these GWAS results with FinnGen GWAS results identified associations with Septic-AKI, which replicated in both independent septic shock cohorts, for cholesterol ester ( p = 4.8 × 10 -44 ), lysophosphatidylcholine ( p = 8.5 × 10 -54 ), phosphatidylcholine ( p = 2.7 × 10 -39 ), and phosphatidylethanolamine ( p = 2.1 × 10 -28 ). CONCLUSIONS: For Septic-AKI, GWAS identified a novel genetic susceptibility locus ( GALNTL6 ), which is also associated with cardiometabolic traits. We then further found that obesity- and lipid-related traits are possible contributors to the pathogenesis of Septic-AKI.
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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".