Biology subjects

Crampin, A. C.

Publications and source records attributed to Crampin, A. C..

3 recordsLinked to original sources

bioRxiv2020

Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans

Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, primarily in populations of European ancestry. We conducted the first GWAS of estimated glomerular filtration rate (eGFR) in Africa in 3288 Ugandans and replicated the findings in 8224 African Americans. We identified two loci associated with eGFR at genome-wide significance (p<5x10-8). The most significantly associated variant (rs2433603, p=2.4x10-9) in GATM was distinct from previously reported signals. A second association signal mapping near HBB (rs141845179, p=3.0x10-8) was not significant after conditioning on a previously reported SNP (rs334) for eGFR. However, fine-mapping analyses highlighted rs141845179 to be the most likely causal variant at the HBB locus (posterior probability of 0.61). A trans-ethnic GRS of eGFR constructed from previously reported lead SNPs was not predictive into the Ugandan population, indicating that additional large-scale efforts in Africa are necessary to gain further insight into the genetic architecture of kidney disease.

genetics↗

bioRxiv2019

Identification of reduced host transcriptomic signatures for tuberculosis and digital PCR-based validation and quantification

Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate the development of diagnostic tests.\n\nTo identify minimal transcript signatures, we applied a novel transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were validated using reverse transcriptase (RT) - digital PCR (dPCR).\n\nA four-transcript signature (GBP6, TMCC1, PRDM1, ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2 - 100%). A three-transcript signature (FCGR1A, ZNF296, C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3 - 100%), regardless of HIV.\n\nThese signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.

molecular biology↗

bioRxiv2019

Sex and area differences in the association between adiposity and lipid profile in Malawi

BackgroundEvidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study aimed to assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence (rural/urban). MethodsData from 12,847 rural and 12,096 urban Malawian residents were used. The associations of body mass index (BMI) and waist-hip ratio (WHR) with fasting lipids (total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprote in-cholesterol (HDL-C) and triglycerides (TG)) were assessed by area and sex. ResultsA great proportion of adults have high BMI and WHR, and this was associated with adverse lipid profiles; higher BMI and WHR were linearly associated with increased TC, LDL-C and TG and reduced HDL-C. BMI was more strongly related to fasting lipids than was WHR. The associations of adiposity with adverse lipid profile were stronger in urban compared with rural residents. ConclusionsThe consistent associations observed of higher adiposity with adverse lipid profiles in females and males living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. Our findings underline the potential utility of BMI in estimating cardiovascular risk and highlight the need for greater investment to understand the long-term health outcomes of obesity and adverse lipid profiles and the extent to which lifestyle changes and treatments effectively prevent and modify adverse cardio-metabolic outcomes. Key messagesO_LIHigher body mass index (BMI) and waist to hip ratio (WHR) are associated with increased total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) and reduced high density lipoprotein-cholesterol (HDL-C) in a large sub-Saharan African population. C_LIO_LITotal adiposity is more strongly associated with adverse lipid profile than central adiposity. C_LIO_LIDespite the higher BMI and the less favourable lipid profile in urban residents, stronger associations between BMI and TC, LDL-C and TG are observed in rural than urban residents. C_LI

epidemiology↗