Browsing by Author "Ananyo Choudhury"

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    Carriers of Heterozygous LossofFunction ACE Mutations Are at Risk for Alzheimers Disease
    S M Danilov; I A Adzhubei; A J Kozuch; P A Petukhov; Ananyo Choudhury; Dhriti Sengupta; E et al
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    Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
    (2022-02-14) Palwende Romuald Boua; Jean-Tristan Brandenburg; Ananyo Choudhury; Hermann Sorgho; Engelbert A Nonterah; Godfred Agongo; Gershim Asiki; Lisa Micklesfield; Solomon Choma; Francesc Xavier Gómez-Olivé; Scott Hazelhurst; Halidou Tinto; Nigel J Crowther; Christopher G Mathew; Michèle Ramsay
    Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.
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    Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.
    (2023-03-27) Cassandra C. Soo; Jean-Tristan Brandenburg; Almut Nebel; Stephen Tollman; Lisa Berkman; Michèle Ramsay; Ananyo Choudhury
    Cognitive function is an indicator for global physical and mental health, and cognitive impairment has been associated with poorer life outcomes and earlier mortality. A standard cognition test, adapted to a rural-dwelling African community, and the Oxford Cognition Screen-Plus were used to capture cognitive performance as five continuous traits (total cognition score, verbal episodic memory, executive function, language, and visuospatial ability) for 2,246 adults in this population of South Africans. A novel common variant, rs73485231, reached genome-wide significance for association with episodic memory using data for ~14 million markers imputed from the H3Africa genotyping array data. Windowbased replication of previously implicated variants and regions of interest support the discovery of African-specific associated variants despite the small population size and low allele frequency. This African genome-wide association study identifies suggestive associations with general cognition and domain-specific cognitive pathways and lays the groundwork for further genomic studies on cognition in Africa.
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    Genomic and environmental risk factors for cardiometabolic diseases in Africa: methods used for Phase 1 of the AWI-Gen population cross-sectional study
    (2018-07-12) Stuart A. Al; Cassandra Soo; Godfred Agongo; Marianne Alberts; Lucas Amenga-Etego; Romuald P. Boua; Ananyo Choudhury; Nigel J. Crowther; Cornelius Depuur; F. Xavier GómezOlivé; Issa Guiraud; Tilahun N. Haregu; Scott Hazelhurst; Kathleen Kahn; Christopher Khayeka-Wandabwa; Catherine Kyobutung; Zané Lombard; Felistas Mashinya; Lisa Micklesfield; Shukri F. Mohamed; Freedom Mukomana; Seydou Nakanabo-Diallo; Hamtandi M. Natama; Nicholas Ngomi; Engelbert A. Nonterah; Shane A. Norris; Abraham R. Oduro; Athanase M. Somé; Hermann Sorgho; Paulina Tindana; Halidou Tinto; Stephen Tollman; Rhian Twine; Alisha Wade; Osman Sankoh; Michèle Ramsay
    There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent
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    Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits
    (2022-05-11) Ananyo Choudhury; Jean-Tristan Brandenburg; Tinashe Chikowore; Dhriti Sengupta; Palwende Romuald Boua; Nigel J. Crowther; Godfred Agongo; Gershim Asik; F. Xavier Gómez-Olivé; Isaac Kisiangani; Eric Maimela; Matshane Masemola-Maphutha; Lisa K. Micklesfield; Engelbert A. Nonterah; Shane A. Norris; Hermann Sorgho; Halidou Tinto; Stephen Tollman; Sarah E. Graham; Cristen J. Willer; AWI-Gen study; H3Africa Consortium; Scott Hazelhurst; Michèle Ramsay
    Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10−8). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10−8). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data.
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    Systematic Review of Genomic Associations with Blood Pressure and Hypertension in Populations with AfricanAncestry
    Surina Singh; Jean-Tristan Brandenburg; Ananyo Choudhury; Francesc Gomez-Olive Casas; Michele Ramsay
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    Trans-ethnic genomic informed risk assessment for Alzeheimer's disease: an International Hundred K+ Cohorts Consortium study.
    (2023-07-14) Patrick M Sleiman; Hui-Qi Qu; John J Connolly; Frank Mentch; Alexandre Pereira; Paulo A Lotufo; Stephen Tollman; Ananyo Choudhury; Michele Ramsay; Norihiro Kato; Kouichi Ozaki; Risa Mitsumori; Jae-Pil Jeon; Chang Hyung Hong; Sang Joon Son; Hyun Woong Roh; Dong-Gi Lee; Naaheed Mukadam; Isabelle F Foote; Charles R Marshall; Adam Butterworth; Bram P Prins; Joseph T Glessner; Hakon Hakonarson
    Background: As a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD). Methods: The GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure. Results: We validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD. Conclusions: As the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.
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    Transethnic genomic informed risk assessment for Alzeheimers disease an international Hundred K and Cohorts Consortium
    PM Sleiman; H-Q Qu; JJ Connolly; F Mentch; Stephen Tollman; Ananyo Choudhury; Michele Ramsay; E et al
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    Transethnic genomic informed risk assessment for Alzheimers disease An International Hundred K Cohorts Consortium study
    P M Sleiman; H Q Qu; J J Connolly; F Mentch; Stephen Tollman; Ananyo Choudhury; Michele Ramsay; E et al