Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Trends and Determinants of Comprehensive Knowledge of HIV among Adolescents and Young Adults in Nigeria: 2003 - 2013

Abstract This study examined comprehensive knowledge of HIV (CKH) and its determinants among young people aged 15-24 years in Nigeria between 2003 and 2013. Secondary analysis was conducted on three rounds of NDHS 2003, 2008 and 2013 data. CKH increased significantly between 2003 and 2013, but the level reached in 2013 fell short of the global expectation for young people. Its significant determinants included gender, age,  educational attainment, place and region of residence, household wealth status and uptake of HIV test. There is need to sustain all on-going  effective youth-focused interventions and programmes to meet the  comprehensive knowledge needs for all young people in Nigeria.Keywords: Young people, HIV and AIDS, Comprehensive knowledge, Nigeria, Determinants Cette étude a examiné la connaissance approfondie du VIH (CCV) et ses déterminants chez les jeunes gens âgés de 15 à 24 ans au Nigeria entre 2003 et 2013. Une analyse secondaire a été menée sur trois séries de données de NDHS 2003, 2008 et 2013. La CCV a augmenté de manière significative entre 2003 et 2013, mais le niveau atteint en 2013 était inférieur aux attentes mondiales pour les jeunes. Ses déterminants importants comprennent le genre, l'âge, le niveau de scolarité, le lieu et la région de résidence, l'état de la richesse des ménages et l'adoption de l‘analyse pour le dépistage du VIH. Il est nécessaire de soutenir toutes les interventions et programmes efficaces axés sur les jeunes pour répondre aux besoins globaux en connaissances de tous les jeunes du Nigeria Mots-clés: Jeunes, VIH et SIDA, connaissance compréhensive, Nigeria, déterminant

Prevalence of Internalized Homophobia and HIV Associated Risks among Men who have Sex with Men in Nigeria

This study assessed the level of internalized homophobia and associated factors among men who have sex with men (MSM) in Nigeria. Using respondent driven sampling, MSM were recruited in Lagos and Ibadan between July and September, 2006. Internalized homophobia was assessed as a negative composite score using an 11-item scale. A total of 1,125 MSM were interviewed. About 44.4% self-identified as homosexual or gay while 55% regarded themselves as bisexual. About a third of the respondents reported internalized homophobia. With homosexual/gay men as reference, respondents who self-identified as bisexual were two times more likely [AOR 2.1; 95 CI: 1.6 – 2.9, p<0.001] to report internalized homophobia. Those who were HIV positive were also twice as likely to report internalized homophobia compared to those who were HIV negative [AOR 1.8; 95% CI: 1.2 – 2.7, p=0.004]. As internalized homophobia impedes acceptance of HIV prevention programming, identifying MSM who experience internalized homophobia is integral to the success of HIV prevention programming in NigeriaCette étude a évalué le niveau de l&apos;homophobie intériorisée et les facteurs qui y sont liés chez les hommes qui ont des rapports sexuels avec des hommes (HSH) au Nigeria. A l’aide d&apos;un échantillonnage basé sur les interviews, les HSH ont été recrutés à Lagos et à Ibadan entre les mois de juillet et septembre, 2006. L&apos;homophobie intériorisée a été évaluée par un indice négatif composite en utilisant une échelle de 11 items. Au total, 1.125 HSH ont été interviewés. À peu près 44,4% se sont identifiés comme des homosexuels tandis que 55% se considéraient comme des bisexuels. Environ un tiers des interviewés ont signalé l&apos;homophobie intériorisée. En se servant des hommes homosexuels comme référence, les interviewés qui se sont identifiés comme bisexuels avaient deux fois plus la possibilité [AOR 2,1; IC 95: 1,6 - 2,9, p <0,001] de signaler l&apos;homophobie intériorisée. Ceux qui étaient séropositifs avaient également deux fois plus la possibilité de signaler l&apos;homophobie intériorisée par rapport à ceux qui étaient séronégatifs [AOR: 1,8; IC à 95%: 1,2 - 2,7, p = 0,004]. Etant donné que l&apos;homophobie intériorisée empêche l&apos;acceptation de la prévention de la programmation du VIH, l&apos;identification des HSH qui éprouvent l&apos;homophobie intériorisée fait partie intégrante de la réussite de la prévention de la programmation du VIH au Nigéri

A profile on HIV prevalence and risk behaviors among injecting drug users in Nigeria: Should we be alarmed?

Objective: Injecting drug use is now recognized as a significant risk factor for HIV in sub-Saharan Africa. We evaluated prevalence and correlates of HIV among injecting drug users (IDUs) in Nigeria. Methods: A cross sectional design using respondent driven sampling was conducted in six states in 2010. Weighted HIV prevalence and injecting risk behaviors calculated using RDS analytic tool. Logistic regression was used to determine correlates of HIV infection, stratified by state. Results: Total numbers of IDUs ranged from 197 in Lagos to 273 in Cross River and Oyo states. HIV prevalence was highest in Federal Capital Territory (FCT) at 9.3%, Kaduna 5.8%, Oyo 5.1%, Kano 4.9%, CR 3.3% and Lagos 3.0%. Although \u3e 90% of participants were male, females had higher HIV prevalence in all states surveyed except FCT (range: 7.4% in CR to 37.7% in Kano). Logistic regression showed that females were significantly more likely to be HIV positive in Kano [OR = 33.2, 95% CI: 6.8–160.4], Oyo [AOR = 15.9, 95% CI: 3.69–68.51], Lagos [OR = 15.5, 95% CI: 2.41–99.5] and Kaduna states [AOR = 19.6, 95% CI: 4.4–87.6]. For injecting risk behavior, only receptive sharing was associated with HIV [AOR = 7.6, 95% CI: 1.2–48.7] and [AOR = 0.2, 95% CI: 0.04–0.92] in Oyo and Kaduna states respectively. Conclusions: Considerable heterogeneity in the prevalence of HIV and associated risk behaviors exist among IDUs across Nigeria. Females had higher HIV prevalence among IDUs in five of six states, suggesting a need for targeted interventions for this hidden subgroup. Further research is needed to understand HIV transmission dynamics of IDUs in Nigeria. Community-based opioid substitution therapy and needle exchange programs should be implemented without delay

Population-based prevalence of hepatitis B and C virus, HIV, syphilis, gonorrhoea and chlamydia in male injection drug users in Lagos, Nigeria

There is little research on injecting drug use in Nigeria. We investigated the prevalence of HIV, hepatitis B and C, and sexually transmitted infections (STIs) among male injection drug users (IDUs) in Lagos. Male IDUs (N 328) were recruited through respondent-driven sampling. Participants completed an interview about their sexual and injecting risk behaviours and were tested for hepatitis B surface antigen (HBV), hepatitis C antibody (HCV), HIV and syphilis, as well as genital chlamydia and gonorrhoea infections. Three-quarters of IDUs (74%) reported injecting drugs in the past one month although most did not share needles (92%) and the majority obtained sterile needles from pharmacists (87%). Estimated HBV, HCV, HIV, syphilis, gonorrhoea and chlamydia prevalences were 7.8%, 7.7%, 0.9%, 1.9%, 0.0%, and 3.7%, respectively. The burden of HIV is presently low among IDUs in Lagos. Changes in accessibility to sterile needles at pharmacists would likely have a deleterious effect on IDUs’ health. HBV vaccination and HCV prevention programmes for IDUs are urgently needed

The effects of centering pregnancy on maternal and fetal outcomes in northern Nigeria; a prospective cohort analysis

Abstract Background Maternal and infant mortality remains high in Nigeria primarily due to low use of skilled birth attendants. Huge disparities exist between southern and northen Nigeria on use of skilled birth attendants with south significantly higher than the north. We assessed the effect of centering pregnancy group (CPG) antenatal care on the uptake of antenatal care (ANC), facility delivery and immunization rates for infants in Kano state. Methods Between December 2012 and May 2014, pregnant women with similar sociodemographics and obstetric history were enrolled into intervention (CPG) and control groups and followed up prospectively. Chi-square tests were conducted to compare the differences between the intervention and the control groups with respect to background characteristics and intervention outcomes. Logistic regression was used to measure the associations between CPG and uptake of services for mother-baby pairs in care. Results A total of 517 (260 in the control group and 257 in the CPG) pregnant women enrolled and participated in the study. Thirty-six percent of women in the control group attended ANC at least once in 2nd and 3nd trimester compared to 49% of respondents in the CPG (p < 0.01). Health facility delivery was higher among CPG (13% vs. 8%; p < 0.01). When controlled for age, number of previous pregnancies, number of term deliveries, number of children alive and occupation of respondent or their spouses, respondents who participated in the CPGs compared to those who did not, were more likely to attend at least one antenatal care (ANC) session in the third trimester [adjusted risk ratio (ARR):1.52; 95% CI:1.36–1.69], more likely to immunize their babies at six weeks [ARR: 2.23; 95% CI: 1.16–4.29] and fourteen weeks [ARR: 3.46; 95% CI: 1.19–10.01] and more likely to use health services [ARR: 1.50; 95% CI: 1.06–2.13]. Conclusion Centering or group pregnancy showed a positive effect on the use of antenatal services, facility delivery and postnatal services and thus is a promising intervention to increase uptake of maternal health care services in northern Nigeria. The low facility delivery remains a cause for alarm and requires further investigation to improve facility delivery in northern Nigeria

Prevalence and factors associated with anogenital warts among sexual and gender minorities attending a trusted community health center in Lagos, Nigeria.

Anogenital warts caused by human papillomavirus are common in sexual and gender minorities (SGM). The prevalence of, and factors associated with warts were described for SGM with a high burden of HIV in Nigeria. Individuals who reported anal sex with men were enrolled in the TRUST/RV368 cohort. Participants completed an interviewer-led survey, provided biological samples, and had a physical examination. Specific to the Lagos site, clinic staff offered standardized warts treatment services. RDS-weighted multivariable logistic regression was used to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors potentially associated with anogenital warts. Of 672 enrolled SGM, 478 (71%) engaged in warts services and had complete data. The median age (interquartile range) was 22 (20-26) years, 272 (52%) initiated sex before age 18, and 347 (79%) were cisgender men. Multiple male sexual partners in the previous year were reported by 448 (90%) of the participants, and 342 (66%) were living with HIV. Warts were diagnosed in 252 (54%), including anal warts in 234 (43%) and penile warts in 44 (8%); 26 (5%) had both anal and penile warts. Factors independently associated with warts included HIV (AOR:2.97; CI:1.44-6.14), engaging in receptive anal sex (AOR:3.49; CI:1.25-9.75), having multiple male sexual partners (AOR:7.26; CI:2.11-24.87), age at sexual debut (AOR:0.53; CI:0.28-0.98), and non-binary gender identity (AOR:0.20; CI:0.05-0.71). Warts were common among SGM in Nigeria, particularly those living with HIV. Administration of HPV vaccination before sexual debut or as a catch-up vaccination may prevent HPV-associated complications

HIV status disclosure by Nigerian men who have sex with men and transgender women living with HIV: A cross-sectional analysis at enrollment into an observational cohort

Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionately impacted by HIV and may face barriers to HIV status disclosure with negative ramifications for HIV prevention and care. We evaluated HIV status disclosure to sexual partners, HIV treatment outcomes, and stigma patterns of MSM and TGW in Abuja and Lagos, Nigeria. Methods: Previously-diagnosed MSM and TGW living with HIV who enrolled in the TRUST/RV368 cohort from March 2013 to August 2018 were asked, “Have you told your (male/female) sexual partners (MSP/FSP) that you are living with HIV?” In separate analyses, robust Poisson regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (95% CIs) for characteristics associated with HIV status disclosure to MSP and FSP. Self-reported stigma indicators were compared between groups. Results: Of 493 participants living with HIV, 153 (31.0%) had disclosed their HIV status to some or all MSP since being diagnosed. Among 222 with FSP, 34 (15.3%) had disclosed to some or all FSP. Factors independently associated with disclosure to MSP included living in Lagos (RR 1.58 [95% CI 1.14–2.20]) and having viral load \u3c 50 copies/mL (RR 1.67 [95% CI 1.24–2.25]). Disclosure to FSP was more common among participants who were working in entertainment industries (RR 6.25 [95% CI 1.06–36.84]) or as drivers/laborers (RR 6.66 [95% CI 1.10–40.36], as compared to unemployed) and also among those married/cohabiting (RR 3.95 [95% CI 1.97–7.91], as compared to single) and prescribed ART (RR 2.27 [95% CI 1.07–4.83]). No differences in self-reported stigma indicators were observed by disclosure status to MSP but disclosure to FSP was associated with a lower likelihood of ever having been assaulted (26.5% versus 45.2%, p = 0.042). Conclusions: HIV status disclosure to sexual partners was uncommon among Nigerian MSM and TGW living with HIV but was associated with improved HIV care outcomes. Disclosure was not associated with substantially increased experiences of stigma. Strategies to encourage HIV status disclosure may improve HIV management outcomes in these highly-marginalized populations with a high burden of HIV infection

Sensitivity comparison of sociodemographic and sexual behaviour factors between SGM included and excluded from the analyses.

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