A multivariable Mendelian randomization analysis disentangling the causal relations between abdominal obesity, non-alcoholic fatty liver disease and cardiometabolic diseases
Bibliographic record
Abstract
Abstract Background Observational studies have linked obesity and especially abdominal obesity to non-alcoholic fatty liver disease (NAFLD). These traits are also associated with type 2 diabetes (T2D) and coronary artery disease (CAD) but the causal factor(s) underlying these associations remain unexplored. Methods We used a multivariable Mendelian randomization (MVMR) study design to determine whether obesity (defined using body mass index [BMI]) and abdominal obesity (defined using waist circumference) were causally associated with NAFLD using publicly available genome-wide association study (GWAS) summary statistics of the UK Biobank (n>450,000) and a GWAS meta-analysis of NAFLD (8434 cases and 770,180 control). A MVMR study design was also used to determine the respective causal contributions of waist circumference and NAFLD to T2D and CAD using additional GWAS summary statistics of the DIAGRAM (74,124 cases and 824,006 controls) and CARDIoGRAMplusC4D (122,733 cases and 424,528 controls) consortia. Results In univariable Mendelian randomization analyses, both BMI and waist circumference were associated with NAFLD. NAFLD was not associated with obesity or abdominal obesity. In MVMR analyses, waist circumference was associated with NAFLD when accounting for BMI (OR per 1-standard deviation increase = 2.56 95% CI: 1.39-4.69, p=2.4e-03) and BMI was not associated with NAFLD when accounting for waist circumference (0.81 95% CI: 0.5-1.31, p =3.9e-01). In MVMR analyses accounting for NAFLD, waist circumference remained strongly associated with both T2D (3.25 95% CI: 2.87-3.68, p=5.1e-77) and CAD (1.62 95% CI: 1.48-1.76, p=6.5e-28). Conclusions These results identified abdominal obesity as a strong, independent and causal contributor to NAFLD, T2D and CAD, suggesting that interventions targeting abdominal obesity rather than body weight per se should be prioritized for the prevention and management of cardiometabolic diseases.
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 | 0.044 | 0.063 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.011 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 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".