Genome-wide association study and meta-analysis of phytosterols identifies a novel locus for serum levels of campesterol.

Autor: Alenbawi J; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar., Al-Sarraj YA; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar.; Qatar Genome Program (QGP), Qatar Foundation Research, Development and Innovation, Qatar Foundation (QF), P.O. Box 5825, Doha, Qatar., Umlai UI; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar., Kadhi A; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar.; College of Health and Sciences, University of Doha for Science and Technology, P.O. Box 24449, Doha, Qatar., Hendi NN; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar., Nemer G; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar. gnemer@hbku.edu.qa., Albagha OME; Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar. oalbagha@hbku.edu.qa.; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. oalbagha@hbku.edu.qa.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2024 Aug 01; Vol. 18 (1), pp. 85. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1186/s40246-024-00649-x
Abstrakt: Sitosterolemia is a rare inherited disorder caused by mutations in the ABCG5/ABCG8 genes. These genes encode proteins involved in the transport of plant sterols. Mutations in these genes lead to decreased excretion of phytosterols, which can accumulate in the body and lead to a variety of health problems, including premature coronary artery disease. We conducted the first genome-wide association study (GWAS) in the Middle East/North Africa population to identify genetic determinants of plant sterol levels in Qatari people. GWAS was performed on serum levels of β-sitosterol and campesterol using the Metabolon platform from Qatar Biobank (QBB) and genome sequence data provided by Qatar Genome Program. A trans-ancestry meta-analysis of data from our Qatari cohort with summary statistics from a previously published large cohort (9758 subjects) of European ancestry was conducted. Using conditional analysis, we identified two independent single nucleotide polymorphisms associated with β-sitosterol (rs145164937 and rs4299376), and two others with campesterol (rs7598542 and rs75901165) in the Qatari population in addition to previously reported variants. All of them map to the ABCG5/8 locus except rs75901165 which is located within the Intraflagellar Transport 43 (IFT43) gene. The meta-analysis replicated most of the reported variants, and our study provided significant support for the association of variants in SCARB1 and ABO with sitosterolemia. Evaluation of a polygenic risk score devised from European GWAS data showed moderate performance when applied to QBB (adjusted-R 2  = 0.082). These findings provide new insights into the genetic architecture of phytosterol metabolism while showing the importance including under-represented populations in future GWAS studies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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