Additional file 2 of Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization
Bibliographic record
Abstract
Additional file 2: Supplementary information and Supplementary Tables and Figures. Table S1. Univariable Mendelian randomization results for age at first sex and number of sexual partners on risk of oropharyngeal cancer using a more stringent r2 < 0.001. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; IVW, inverse variance weighted; SE, standard error; OR, odds ratio; CI, confidence intervals; SNPs, single nucleotide polymorphisms. NSP OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD increase (0.94) in number of sexual partners. AFS OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD change (7.3-month delay) in age at first sex. Table S2. Univariable Mendelian randomization results of age at first sex with HPV seropositivity including sensitivity analyses. Abbreviations: IVW, inverse variance weighted; SE, standard error; OR, odds ratio; CI, confidence intervals; SNPs, single nucleotide polymorphisms. OR represents the exponential change in odds of HPV seropositivity per SD change (7.3-month delay) in age at first sex. GWAS were run for four HPV markers derived from UK Biobank, with HPV16 seropositivity described: if antigen L1 > 175; if antigen E6 > 120 or antigen E7 > 150. Table S3. Mendelian randomization results of number of sexual partners with HPV seropositivity including sensitivity analyses. Abbreviations: IVW, inverse variance weighted; SE, standard error; OR, odds ratio; CI, confidence intervals; SNPs, single nucleotide polymorphisms. OR represents the exponential change in odds of HPV seropositivity per SD increase (0.94) in number of sexual partners. GWAS were run for four HPV markers derived from UK Biobank, with HPV16 seropositivity described: if antigen L1 > 175; if antigen E6 > 120 or antigen E7 > 150. Table S4. Assessing weak instrument bias (F-statistic) and proportion of variance in the phenotype (R2) explained by age at first sex and number of sexual partners genetic instruments. Abbreviations: AFS, age at first sex; NSP, number of sexual partners. Table S5. Assessing heterogeneity and directional pleiotropy of single nucleotide polymorphism effect estimates for age at first sex and number of sexual partners on oropharyngeal cancer risk. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; Q, Cochran’s Q-statistic; df, degrees of freedom; SE, standard error; P, p-value. Table S6. MR-PRESSO outliers detected results for age at first sex and number of sexual partners instruments on oropharyngeal cancer risk. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; Q-stat, Cochran’s Q statistic. Table S7. MR-PRESSO results for age at first sex and number of sexual partners instruments on oropharyngeal cancer risk. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; RSSobs, residual sum of squares observations. Table S8. Outlier corrected results for age at first sex and number of sexual partners instruments on combined oropharyngeal cancer. Abbreviations: IVW, inverse variance weighted; OR, odds ratio; CI, confidence intervals; SNPs, single nucleotide polymorphisms. NSP OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD increase (0.94) in number of sexual partners. AFS OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD change (7.3-month delay) in age at first sex. Table S9. SIMEX correction MR-Egger regression results for age at first sex and number of sexual partners instruments on oropharyngeal cancer risk (where I2 < 0.90). Abbreviations: AFS, age at first sex; NSP, number of sexual partners; I2, I-squared statistic; OR, odds ratio; CI, confidence intervals; P, p-value. Table S10. Univariable Mendelian randomization examining effects of age at first sex on positive and negative controls. Abbreviations: SE, standard error; OR, odds ratio; P, p-value; CI, confidence intervals; AFS, age at first sex. AFS OR represents the exponential change in odds of cervical or lung cancer per SD change (7.3-month delay) in age at first sex. Table S11. Univariable Mendelian randomization examining effects of number of sexual partners on positive and negative controls. Abbreviations: SE, standard error; OR, odds ratio; P, p-value; CI, confidence intervals; NSP, number of sexual partners; NSP OR represents the exponential change in odds of cervical or lung cancer per SD increase (0.94) in number of sexual partners. Table S12. Assessing directional pleiotropy through MR-Egger intercept for univariable MR positive and negative control analyses. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; SE, standard error; P, p-value. Table S13. Assessing heterogeneity of single nucleotide polymorphism effect estimates in inverse variance weighted and MR-Egger regression for univariable MR positive and negative control analyses. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; Q, Cochran’s Q-statistic; IVW, inverse variance weighted; df, degrees of freedom; P, p-value. Table S14. MR-PRESSO outliers detected results for age at first sex and number of sexual partners instruments on positive and negative controls. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; Q-stat, Cochran’s Q statistic. Table S15. Outlier corrected results for age at first sex and number of sexual partners instruments on positive and negative controls. Abbreviations: SE, standard error; OR, odds ratio; P, p-value; CI, confidence intervals; AFS, age at first sex; NSP, number of sexual partners. AFS OR represents the exponential change in odds of cervical or lung cancer per SD change (7.3-month delay) in age at first sex. NSP OR represents the exponential change in odds cervical or lung cancer per SD increase (0.94) in number of sexual partners. Table S16. Causal Analysis Using Summary Effect estimates (CAUSE) results for age at first sex on risk of oropharyngeal cancer. Abbreviations: OPC, oropharyngeal cancer; ELPD, expected log pointwise posterior density; se, standard error; γ (gamma), estimate of causal effect if causal model is correct; η (eta), estimate of correlated pleiotropy; q, proportion of effect due to correlated pleiotropy; CI, confidence intervals; NA, non-applicable. Table S17. Causal Analysis Using Summary Effect estimates (CAUSE) results for number of sexual partners on risk of oropharyngeal cancer. Abbreviations: OPC, oropharyngeal cancer; ELPD, expected log pointwise posterior density; se, standard error; γ (gamma), estimate of causal effect if causal model is correct; η (eta), estimate of correlated pleiotropy; q, proportion of effect due to correlated pleiotropy; CI, confidence intervals; NA, non-applicable. Table S18. Overlapping single nucleotide polymorphisms identified between genetic instruments used in multivariable Mendelian randomization. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; RT, risk tolerance; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week. Table S19. LD Score Regression results for all exposures. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week; RT, risk tolerance; rg, genetic correlation; SE, bootstrap standard error of genetic correlation, h2 obs = estimated SNP heritability of the second exposure , h2 obs se = bootstrap standard error of the SNP heritability estimate, h2 int = LD score regression intercept for the second exposure, h2 int se = bootstrap standard error of the intercept, gcov int = estimated genetic covariance between exposure 1 and 2, gcov int se = bootstrap standard error of the genetic covariance. Table S20. Assessing directional pleiotropy through MR-Egger intercept for multivariable MR analysis on oropharyngeal cancer. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; SE, standard error; P, p-value; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week; RT, risk tolerance. Table S21. Bidirectional Mendelian randomization analysis for age at first sex on other risk factors. Abbreviations: AFS, age at first sex; SNP, single nucleotide polymorphism; SE, standard error; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week; RT, risk tolerance; EA, educational attainment. Table S22. Bidirectional Mendelian randomization analysis for number of sexual partners on other risk factors. Abbreviations: NSP, number of sexual partners; SNP, single nucleotide polymorphism; SE, standard error; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week; RT, risk tolerance; EA, educational attainment. Table S23. Multivariable Mendelian randomization for age at first sex and number of sexual partners with risk lung cancer. Abbreviations: IVW, inverse variance weighted; OR, odds ratio; CI, confidence intervals; P, p-value; Q-stat, Cochran’s Q statistic; F-stat, conditional F-statistic. AFS OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD change (7.3-month delay) in age at first sex. NSP OR represents the exponential change in odds of oropharyngeal squamous cell carcinoma per SD increase (0.94) in number of sexual partners. Table S24. Assessing directional pleiotropy through MR-Egger intercept for multivariable MR analysis on lung and cervical cancer. Abbreviations: AFS, age at first sex; NSP, number of sexual partners; SE, standard error; P, p-value; CSI, comprehensive smoking index; SI, smoking initiation; DPW, drinks per week; RT, risk tolerance. Figure S1 Forest plots showing Mendelian randomization results for age at first sex and number of sexual partners single nucleotide polymorphisms with risk of oropharyngeal cancer in GAME-ON. Effect estimates are reported on the log odds scale with 95% confidence
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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 | 0.015 | 0.147 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.004 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.850 | 0.077 |
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".