2. Academic Validation
  3. OSBPL11 is an African-specific locus associated with 25-hydroxyvitamin D concentrations and cardiometabolic health

OSBPL11 is an African-specific locus associated with 25-hydroxyvitamin D concentrations and cardiometabolic health

  • medRxiv. 2025 May 31:2025.05.27.25328359. doi: 10.1101/2025.05.27.25328359.
Reagan M Mogire 1 2,  John Muthii Muriuki 1,  Ruth Fiona Bayimenye 3,  Alexander J Mentzer 4 5,  Amanda Chong 4,  Mateus H Gouveia 2,  Amy R Bentley 2,  Gavin Band 4,  Pauline King'ori 1,  Ruth Mitchell 6,  Emily L Webb 7,  Dhriti Sengupta 8,  Lynette Ekunwe 9,  Francis M Ndungu 1,  Alireza Morovat 10,  Alex W Macharia 1,  Clare L Cutland 11,  Gibran Hemani 6,  Sodiomon B Sirima 12,  Michèle Ramsay 8 13,  Camila A Figueiredo 14,  Andrew M Prentice 15,  Shabir A Madhi 16,  Laura M Raffield 17,  Manjinder S Sandhu 18,  Philip Bejon 1 19,  George Davey Smith 6,  Alison M Elliott 20,  Thomas N Williams 1 21,  Charles Rotimi 2,  Christina R Bourne 22,  Anthony Burgett 3,  Adebowale Adeyemo 2,  Sarah H Atkinson 1 19 2
Affiliations

Affiliations

  • 1 Centre for Geographic Medicine Research-Coast, KEMRI-Wellcome Trust Research Programme, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya.
  • 2 Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
  • 3 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117 USA.
  • 4 Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK.
  • 5 Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
  • 6 Medical Research Council (MRC) Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • 7 MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
  • 8 Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
  • 9 Department of Medicine, University of MS Medical Center (UMMC), Jackson, MS 39213, USA.
  • 10 Department of Clinical Biochemistry, Oxford University Hospitals, Oxford, UK.
  • 11 African Leadership in Vaccinology Expertise (Alive), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • 12 Centre de Recherche Action en Sante (GRAS), 06 BP 10248, Ouagadougou 06, Burkina Faso.
  • 13 Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • 14 Departamento de Ciências da Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, 40110-100, Salvador, Bahia, Brazil.
  • 15 MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
  • 16 South African Medical Research Council: Vaccines and Infectious Diseases Analytical Research Unit (VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • 17 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 18 Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, UK.
  • 19 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • 20 Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
  • 21 Institute of Global Health Innovation, Department of Surgery and Cancer, Imperial College, London, UK.
  • 22 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
PMID: 40492082 DOI: 10.1101/2025.05.27.25328359
Abstract

Vitamin D deficiency is prevalent in Africa, but its genetic determinants are understudied. We report a genome-wide analysis of 25-hydroxyvitamin D (25(OH)D) concentrations in 3670 children from five countries across Africa with replication in four diaspora African ancestry populations (n=21,610). We identify a previously unreported locus at genome-wide significance in West African populations: OSBPL11 (Oxysterol Binding Protein Like 11, lead variant, rs2979356, p=8.01 × 10-9). In vitro and molecular docking assays showed that OSBPL11 is a vitamin D binding protein likely involved in the intracellular binding of vitamin D metabolites. OSBPL11 knockdown mice have increased fat, reduced triglycerides and improved glucose tolerance, and rs2979356 was associated with cardiometabolic health in adults of African ancestry. We also identify previously reported loci determining vitamin D status. Our study advances understanding of vitamin D genetics in Africa and indicates a novel function for OSBPL11 in intracellular binding and transport of vitamin D metabolites.

Keywords

25-hydroxyvitamin D; Africa; GWAS; OSBPL11; Vitamin D; oxysterol.

Figures
Products