METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.
RESULTS: In European ancestry samples, 14 genes were significantly associated (q
RESULTS: We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans.
CONCLUSIONS: We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.
Aim: To evaluate parameters of the proximal tibia geometry amongst the Igbos of South Eastern Nigeria and discuss the clinical implications in total knee replacement.
Methods: The proximal tibia parameters of 558 adult tibiae bones, 300 right-sided and 258 left-sided, collected from the osteological unit of the department of anatomy University of Nigeria Enugu campus were measured using a Venier calipers.
Results: The values of the determined parameters are as follows: anterior posterior dimension (APD): 5.50 cm, medial lateral dimension (MLD):7.53 ± 5.56 cm, proximal length (PL): 7.32 ± 0.67 cm, proximal width (PW) CM: 4.10 ± 0.30 cm, medial tibia posterior slope (MTPS):11.36 ± 4.15° and lateral tibia posterior slope (LTPS):5.65 ± 2.72°. The correlation test between these parameters of the proximal tibia shows a strong significant correlation between LPTS and MPTS (r =0.814, P < .001). The comparison of the means of the MPTS of both sides using independent samples t test shows a mean difference that is not significant (p =0.628). A comparison of the values with other populations shows significant mean difference for MLD with that of Chinese and American populations (p < .05). The mean difference between the APD of this study and the Chinese is significant (p =0.007). A comparison of MPTS and LPTS for Malaysian, Chinese, and white Americans shows a significance difference for all the three populations (p
METHODS AND RESULTS: This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.
CONCLUSIONS: Among Africans with HF, statin treatment was associated with significant reduction in mortality.
METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.
RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.
CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.