Causal effect of age first had sexual intercourse and lifetime number of sexual partners on cervical cancer.

Objective: In this study, we aimed to investigate whether age first had sexual intercourse (AFSI) and lifetime number of sexual partners (LNSP) have a direct causal effect on cervical cancer by Mendelian randomization (MR) analysis. Methods: Four approaches were used for MR Analysis, including MR-Egger, weighted method, weighted median, and inverse variance weighted (IVW). MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) as well as MR-Egger regression analysis were conducted to detect whether there was pleiotropy between IVs and outcome, and the outlier SNPs can be detected by MR-PRESSO. The presence or absence of heterogeneity among IVs was suggested according to Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify and remove SNPs which could independently change the results. We corrected the results using Bonferroni correction. Results: From the results of IVW, AFSI had a negative effect on cervical cancer (OR = 0.996, 95 % CI: 0.995, 0.998 P = 1.70E-07), which still persisted after Bonferroni correction. However, no causal effect of LNSP on cervical cancer was found according to the IVW results (OR = 1.003, 95 % CI: 1.000, 1.007, P = 0.071). From the results of MR-PRESSO and MR-Egger, no SNP with horizontal pleiotropy between cervical cancer was detected and no SNP was identified as an outlier SNP. Cochran's Q statistic suggested that no heterogeneity existed among IVs of AFSI and LNSP. According to Leave-one-out analysis, the results of MR did not change after excluding any single IV. Conclusion: This MR study reveals that early AFSI has a causal effect on cervical cancer.

Association of age at first sexual intercourse and lifetime number of sexual partners with cardiovascular diseases: a bi-directional Mendelian randomization study.

Background: Limited studies have explored the association between sexual factors [age at first sexual intercourse (AFS) and lifetime number of sexual partners (LNSP)] and cardiovascular diseases (CVDs), leaving the causality inconclusive. Methods: We performed a bi-directional Mendelian randomization (MR) study to investigate the causality between sexual factors and CVDs, including coronary artery disease, myocardial infarction, atrial fibrillation (AF), heart failure (HF), and ischemic stroke (IS). Single-nucleotide polymorphisms (SNPs) for sexual factors were extracted from the UK Biobank. Statistics for each CVD were derived from two different databases. MR estimates were calculated per outcome database and were combined through meta-analysis. Several complementary sensitivity analyses were also performed. Results: The primary analysis suggested that AFS was causally associated with the risk of CVDs; the odds ratios (ORs) ranged from 0.686 [95% confidence interval (CI), 0.611-0.770] for HF to 0.798 (95% CI, 0.719-0.886) for AF. However, the association between AFS and IS (OR, 0.844; 95% CI, 0.632-1.126) was not consistent in the meta-analysis after excluding SNPs related to confounders. Moreover, non-significant associations were found between LNSP and CVDs. Reverse direction MR analysis showed that CVDs were not associated with sexual factors. Conclusions: Genetic evidence suggested that AFS was causally associated with the risk of CVDs except for IS, whereas non-significant association of LNSP with CVDs was detected. Further investigation into AFS could be warranted in preventing the progression of CVDs.

Understanding the link between early sexual initiation and later sexually transmitted infection: test and replication in two longitudinal studies.

PURPOSE: Age at sexual initiation is strongly associated with sexually transmitted infections (STI); yet, prevention programs aiming to delay sexual initiation have shown mixed results in reducing STI. This study tested three explanatory mechanisms for the relationship between early sexual debut and STI: number of sexual partners, individual characteristics, and environmental antecedents. METHODS: A test-and-replicate strategy was employed using two longitudinal studies: the Seattle Social Development Project (SSDP) and Raising Healthy Children (RHC). Childhood measures included pubertal age, behavioral disinhibition, and family, school, and peer influences. Alcohol use and age of sexual debut were measured during adolescence. Lifetime number of sexual partners and having sex under the influence were measured during young adulthood. Sexually transmitted infection diagnosis was self-reported at age 24. Early sex was defined as debut at <15 years. Path models were developed in SSDP evaluating relationships between measures, and were then tested in RHC. RESULTS: The relationship between early sex and STI was fully mediated by lifetime sex partners in SSDP, but only partially in RHC, after accounting for co-occurring factors. Behavioral disinhibition predicted early sex, early alcohol use, number of sexual partners, and sex under the influence, but had no direct effect on STI. Family management protected against early sex and early alcohol use, whereas antisocial peers exacerbated the risk. CONCLUSIONS: Early sexual initiation, a key mediator of STI, is driven by antecedents that influence multiple risk behaviors. Targeting co-occurring individual and environmental factors may be more effective than discouraging early sexual debut and may concomitantly improve other risk behaviors.