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

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

Substance Abuse and its Prevalence Among Secondary School Adolescents in Kagoro, Kaduna State, Nigeria

Despite the existing scanty data on patterns of drug abuse in specific groups in the Nigerian communities due to the tendency of changing patterns in illicit drug use with various alarming reports on same points to the need to constantly update information on the use of drugs among Nigerian adolescents. This was a cross sectional, descriptive study on the prevalence of substance use amongst adolescents. A total number of 400 Senior Secondary Schools 1,2,3 students from two selected schools in Kagoro Chiefdom of Kaura local government area in Kaduna State (Nigeria) were randomly administered with a pre-coded four sections (socio-demographic information, drug awareness and use, attitude of the students to drug abuse and practice of substance abuse). Out of a total of 400 respondents, which males constituted 75% and females 25% of substance users. 89.20% were aware of substance use and 10.80 % were not aware. Substances used were alcohol (52.58%), analgesics (33.7%), marijuana (2.59%), cigarette (1.72%), glue/solution (0.86%) and other local substances (8.62%) respectively. Family setting of respondents taking substance (66.6%:5.95%:27.4%) from monogamous, polygamous and extended families respectively. Factors responsible for engagement in substance use was curiosity 38.10%, peer pressure 19.05%, depression 7.14%, energy for work 4.76%, home problems 1.19%, festivities aura 11.90% beliefs 5.96%, others 11.90%. 58.3% of respondents were introduced to substance use by friends, while 25% were introduced by their family members. Curiosity and peer pressure which is a characteristic of this age group are the major reasons for indulgence in substance use as well the ease at obtaining substances. Family also plays a role.nbs