High-depth African genomes inform human migration and health.

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as 'likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.

Association between Serum Folate and Vaginal High-Risk Human Papillomavirus Infections in United States Women.

BACKGROUND: Serum concentration of folate was inversely associated with cervical intraepithelial neoplasia and cervical cancer in some studies. The association between folate and human papillomavirus (HPV) infection, a necessary cause of cervical cancer, has not been well elucidated. OBJECTIVES: We evaluated whether serum folate concentrations were associated with high-risk HPV (hrHPV) infection. METHODS: The study population was 11,801 females, aged 18-59 y, enrolled in the National Health and Nutrition Examination Survey (NHANES), from 2003 to 2016, in the United States. In this cross-sectional study, prevalence ratios (PRs) of vaginal hrHPV were calculated using logistic regression models, by quintiles of serum folate. RESULTS: Females in the lowest quintile had <21.3 nmol/L of folate. Approximately 23% of the females (2733/11,801) were hrHPV positive. In age-adjusted models, folate was significantly associated with hrHPV infection. The PRs and 95% confidence intervals (CIs) were (PR: 1.52; 95% CI: 1.37, 1.70) for the first, (PR: 1.29; 95% CI: 1.15, 1.44) for the second, (PR: 1.19; 95% CI: 1.06, 1.34) for the third, and (PR: 1.09; 95% CI: 0.96, 1.23) for the fourth quintiles, compared with the females in the highest quintile, with a significant P value for trend, <0.0001. The association remained statistically significant after the models were further adjusted for lifestyle and sexual risk factors for hrHPV infection; the females in the lowest quintile were more likely to have hrHPV infection than those in the highest quintile (PR: 1.40; 95% CI: 1.11, 1.53). CONCLUSIONS: Results from this sample of females in the United States suggest that serum folate concentration is inversely associated with hrHPV infection.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

A matched case-control study of bean intake and breast cancer risk in urbanized Nigerian women.

PURPOSE: Bean intake has been associated with reduced risk of breast cancer, however; only a few studies considered molecular subtypes status and none in African women living in Sub-Saharan Africa (SSA). Therefore, the purpose of this study was to examine the associations between dietary intake of beans and breast cancer including its subtypes in Nigerian women. METHODS: Overall, 472 newly diagnosed patients with primary invasive breast cancer were age-matched (± 5 years) with 472 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study from 01/2014 to 07/2016. We collected the dietary intake of beans using a food frequency questionnaire (FFQ). Beans_alone intake was categorized into three levels never (never in the past year), low (≤ 1 portion/week), and high intake (> 1 portion/week). We used conditional and unconditional logistic regression models to estimate the Odds Ratio (OR) and 95% Confidence Intervals (CI) of beans_alone intake and the risk of breast cancer and by its molecular subtypes, respectively. RESULTS: The mean (SD) age of cases was 44.4(10.0) and of controls was 43.5(9.5) years. In the case group, more than half (51.1%) have never consumed beans_alone in the past year compared to 39.0% in the control group. The multivariable models showed inverse associations between beans_alone (high vs. none) and breast cancer (OR = 0.55; 95%CI: 0.36-0.86, p-trend = 0.03), triple-negative (OR = 0.51 95%CI: 0.28-0.95, p-trend = 0.02) and marginally associated with hormone receptor-positive (OR = 0.53, 95%CI: 0.29-0.96, p-trend = 0.06). CONCLUSION: Dietary intake of beans_alone may play a significant role in reducing the incidence of breast cancer, particularly of the more aggressive molecular subtype, triple-negative, in African women living in SSA.

Dietary Intake and Cancer in Sub-Saharan Africa: A Critical Review of Epidemiological Studies.

Cancer incidence is rising rapidly in Sub-Saharan Africa (SSA). Dietary intake is an established risk factor for certain cancers but only a few epidemiological studies have been conducted in SSA. This study systematically reviewed and summarized the published literature on this issue and identified gaps that can be addressed in future research. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and literature searched was conducted until 11/2/2021. Out of the 5,457 potential references, we reviewed 19 eligible studies: 17 case-controls, two cross-sectionals and no cohort study. South Africa and Kenya conducted the majorities of the studies. The commonest studied cancers were esophageal (9/19), colorectal (4/19) and breast (4/19). Only four studies utilized a validated Food Frequency Questionnaire (FFQ). Although most studies (16/19) reported associations between dietary intake and cancer risks, they were lacking important confounders including total energy intake, multivitamin intake, body fat measures, physical-activity, smoking, and alcohol. Despite rapidly expanding cases of cancer associated with diet, the existent evidence on diet-cancer relationship is too scarce to deduce solid conclusions. There is a need for large cohorts with comprehensive datasets, validated dietary instruments while using advanced statistical analyses that can provide further insights into the imperative links between African diet and cancer risk.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2032217 .

Prevalence of vaginal HPV infection among adolescent and early adult girls in Jos, North-Central Nigeria.

PURPOSE: Knowledge of the prevalence of HPV infection among adolescent and early adult girls is essential to determining the best age for the introduction of HPV vaccine, monitoring vaccine efficacy, and giving insight into determinants of persistent high-risk HPV infection, a necessary cause of cervical cancer. Yet, there have been limited studies of HPV infection among adolescent and early adult girls in low-and-middle-income countries. METHODS: In this cross-sectional study, we randomly selected 205 girls, aged 9-20 years, from 10 schools in central Nigeria. We obtained informed consent and assent, collected data, and trained participants to self-collect vaginal samples using swab stick. We genotyped HPV using SPF10-DEIA/LiPA25 and analyzed data using Stata 14®. RESULTS: The mean (SD) age of the girls was 14.9 (2.3) years. We found HPV in 13.2% of vaginal swabs. The earliest age at which anyHPV and hrHPV infections were detected was 10 and 12 years respectively. The prevalence of any HPV peaked at 16 and 17 years, hrHPV at 16 years, lrHPV at 17 and 18 years and multiple hrHPV 18 years of age. The prevalence of hrHPV infection was 1.5% among the 9-12 years age group, 2.9% among 13-16 years and 3.4% among 17-20 years old. The commonest hrHPV types detected were 52 (3.9%), 18 (1.5%) and 51 (2.4%). The most common lrHPV types was 6 (2.9%). CONCLUSION: The prevalence of HPV infection in these urbanized young girls in Nigeria is high and commences after 9 years of age. HPV vaccination in this population should start at 9 years of age or younger to prevent the establishment of persistent HPV infection.

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer.

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination.

Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

BACKGROUND: Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. METHODS: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. RESULTS: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10- 8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10- 6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10- 8), NR5A2 (OR: 3.65, p = 2.03 × 10- 7) and MIR365-2 (OR: 7.71, p = 2.63 × 10- 7) gene regions. CONCLUSIONS: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

Qualitative study of comprehension of heritability in genomics studies among the Yoruba in Nigeria.

BACKGROUND: With growth of genomics research in Africa, concern has arisen about comprehension and adequacy of informed consent given the highly technical terms used in this field. We therefore decided to study whether there are linguistic and cultural concepts used to communicate heritability of characters, traits and diseases in an indigenous African population. METHODS: We conducted Focus Group Discussions among 115 participants stratified by sex, age and socio-economic status and Key Informant Interviews among 25 stakeholders and Key Opinion Leaders among Yoruba living in Ibadan, Nigeria. We used Atlas-ti v.8.3.17 software to analyze the data, using thematic approach. RESULTS: The study participants identified several linguistic and cultural concepts including words, proverbs, and aphorisms that are used to describe heritable characters, traits and diseases in their local dialect. These included words that can be appropriated to describe dominant and recessive traits, variations in penetrance and dilution of strength of heritable characteristics by time and inter-marriage. They also suggested that these traits are transmitted by "blood", and specific partner's blood may be stronger than the other regardless of sex. CONCLUSIONS: Indigenous Yoruba populations have words and linguistic concepts that describe the heritability of characters, traits and diseases which can be appropriated to improve comprehension and adequacy of informed consent in genomics research. Our methods are openly available and can be used by genomic researchers in other African communities.

Prevalence and incidence of genital warts and cervical Human Papillomavirus infections in Nigerian women.

BACKGROUND: Genital warts are important causes of morbidity and their prevalence and incidence can be used to evaluate the impact of HPV vaccination in a population. METHODS: We enrolled 1020 women in a prospective cohort study in Nigeria and followed them for a mean (SD) of 9 (4) months. Nurses conducted pelvic examinations and collected ectocervical samples for HPV testing. We used exact logistic regression models to identify risk factors for genital warts. RESULTS: The mean age of study participants was 38 years, 56% (535/962) were HIV-negative and 44% (427/962) were HIV-positive. Prevalence of genital warts at enrolment was 1% (4/535) among HIV-negative women, and 5% (23/427) among HIV-positive women. Of 614 women (307 HIV negative and 307 HIV positive women) for whom we could compute genital wart incidence, it was 515 (95% CI:13-2872) per 100,000 person-years in HIV-negative and 1370 (95% CI:283-4033) per 100,000 person-years in HIV-positive women. HIV was associated with higher risk of prevalent genital warts (OR:7.14, 95% CI:2.41-28.7, p < 0.001) while higher number of sex partners in the past year was associated with increased risk of incident genital warts (OR:2.86, 95% CI:1.04-6.47. p = 0.04). HPV11 was the only HPV associated with prevalent genital warts in this population (OR:8.21, 95% CI:2.47-27.3, p = 0.001). CONCLUSION: Genital warts are common in Nigeria and our results provide important parameters for monitoring the impact of future HPV vaccination programs in the country. HIV infection and number of sexual partners in past year were important risk factors for prevalent and incident genital warts respectively.

Neurodevelopmental Outcomes of Twins Compared With Singleton Children: A Systematic Review.

More than 200 million children aged <5 years fail to reach their full cognitive potential, and children born as twins are particularly at risk. In this article, we review studies that examined differences in the neurodevelopmental outcomes of twins compared to singletons. We searched the Medline database for articles on twins, singletons, neuro, and cognitive development. We also inspected bibliographies of relevant publications to identify related articles from 2011 to 2017. Our search criteria yielded 162 studies, 8 of which met the inclusion criteria. Of the eight studies examined, four were prospective follow-up studies, three were cross-sectional studies, and one was a randomized controlled trial. Five of these studies were carried out in developed countries, and they found no statistically significant difference in neurodevelopmental outcomes among twins and singletons. However, two of the three studies carried out in developing countries found a difference with singletons having significantly higher academic ratings than twins. Studies in which neurodevelopmental outcomes were measured early in life (1-5 years) showed no significant twin-singleton differences, while those in which it was measured later in life showed mixed twin-singleton differences. Overall, these studies may have been underpowered and may not have been optimally designed and implemented. There is need for studies with adequate sample sizes, good design, and optimal measurement of all relevant covariates in order to resolve the conflicting reports in the literature.

Consumption of processed food dietary patterns in four African populations.

OBJECTIVE: To identify predominant dietary patterns in four African populations and examine their association with obesity. DESIGN: Cross-sectional study.Setting/SubjectsWe used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men. RESULTS: We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern's lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity. CONCLUSIONS: We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

PURPOSE: Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. METHODS: Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. RESULTS: A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). CONCLUSION: Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

Plasma magnesium and risk of ischemic stroke among women.

BACKGROUND AND PURPOSE: Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. METHODS: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989 to 1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status, and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. RESULTS: Median magnesium levels did not differ between ischemic stroke cases and controls (median, 0.86 mmol/L for both; P=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk of 1.34 (95% confidence interval, 0.86-2.10; P trend=0.13) for total ischemic stroke compared with women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels<0.82 mmol/L had significantly greater risk of total ischemic stroke (multivariable relative risk, 1.57; 95% confidence interval, 1.09-2.27; P=0.01) and thrombotic stroke (multivariable relative risk, 1.66; 95% confidence interval, 1.03-2.65; P=0.03) compared with women with magnesium levels≥0.82 mmol/L. No significant effect modification was observed by age, body mass index, hypertension, or diabetes mellitus. CONCLUSIONS: Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women.

Validity and Reproducibility of a Semiquantitative Food Frequency Questionnaire and Food Picture Book in Nigeria.

Background: Increasing noncommunicable diseases in Nigeria are partly related to dietary factors. However, the lack of validated nutrition assessment tools hinders the conduct of nutritional epidemiology research in this population. Objectives: To develop a Food Frequency Questionnaire (FFQ) and Food Picture Book (FPB) for Nigerian adults, and to assess its reproducibility and validity compared with 24-h dietary recalls (24DRs) during different seasons in the year. Methods: We compiled 202 foods for the FFQ through focus groups and consultations with local dietitians. We created an FPB with standardized food portion images to enhance the accuracy of reports of dietary intakes. We administered the FFQs to 205 purposively selected adults in Ibadan, Nigeria at ∼6 monthly intervals between November 2018 and October 2020. We evaluated the FFQ's reproducibility and validity compared with 24DR across the dry and rainy seasons by examining the consumption of common food and mixed dishes. We computed the Spearman's correlation coefficients (SCC), intraclass correlation coefficients (ICC), and Wilcoxon signed-rank tests, and generated Bland and Altman plots. Results: Overall, we studied 110 women (53.7%) and 95 men (46.3%) with a mean age of 45.0 ± 13.4 y (mean ± SD). The reproducibility tests showed a mean ± SD SCC of 0.39 ± 0.14 and mean ± SD ICC of 0.32 ± 0.12. Higher mean ± SD SCC values were noted for cereal products (0.43 ± 0.09), starchy roots and tubers (0.45 ± 0.17), and soups (0.44 ± 0.20). Conversely, lower mean ± SD SCC values were observed for milk products (0.29 ± 0.02), solid fats (0.29 ± 0.26), and fish (0.22 ± 0.19). Regarding validity tests, the overall mean ± SD SCC was 0.27 ± 0.16 and mean ± SD ICC was 0.26 ± 0.16. We observed seasonal variations in intakes of fruits, cassava flour-based products, and nuts, although most foods did not show significant differences in intakes between seasons. Conclusions: Our FFQ and FPB demonstrated moderate correlations and seasonal variations in intakes of certain foods, emphasizing the need to account for seasonality in dietary intakes in nutritional studies in Nigeria and similar countries.

Association Between Cervical Inflammatory Mediators and Prevalent Cervical Human Papillomavirus Infection.

PURPOSE: Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections. MATERIALS AND METHODS: We used a nonmagnetic bead-based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy. RESULTS: The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1ß, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1ß, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections. CONCLUSION: Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.

Correction: A Randomized Controlled Trial to Examine the Relationship Between Peer Mentoring for Physical Activity and Cardiometabolic Health.

[This corrects the article DOI: 10.5334/joc.1268.].

The Impact of Conventional Stroke Risk Factors on Early and Late Onset Ischemic Stroke: a Mendelian Randomization Study.

Objective: Although stroke incidence is decreasing in older ages, it is increasing in young adults. While these divergent trends in stroke incidence are at least partially attributable to diverging prevalence trends in stoke risk factors, age-dependent differences in the impact of stroke risk factors on stroke may also contribute. To address this issue, we utilized Mendelian Randomization (MR) to assess differences in the association of stroke risk factors between early onset ischemic stroke (EOS) and late onset ischemic stroke (LOS). Methods: We employed a two-sample MR design with inverse variance weighting as the primary method of analysis. Using large publicly available genome-wide association summary results, we calculated MR estimates for conventional stroke risk factors (body mass index, total, HDL-and LDL-cholesterol, triglycerides, type 2 diabetes, systolic and diastolic blood pressure, and smoking) in EOS cases (onset 18-59 years, n = 6,728) and controls from the Early Onset Stroke Consortium and in LOS cases (onset ≥ 60 years, n = 9,272) and controls from the Stroke Genetics Network. We then compared odds ratios between EOS and LOS, stratified by TOAST subtypes, to determine if any differences observed between effect sizes could be attributed to differences in the distribution of stroke subtypes. Results: EOS was significantly associated with all risk factors except for total cholesterol levels, and LOS was associated with all risk factors except for triglyceride and total cholesterol levels. The associations of BMI, DBP, SBP, and HDL-cholesterol were significantly stronger in EOS than LOS (all p < 0.004). The differential distribution of stroke subtypes could not explain the difference in effect size observed between EOS and LOS. Conclusion: These results suggest that interventions targeted at lowering body mass index and blood pressure may be particularly important for reducing stroke risk in young adults.

Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.