دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Genome-wide association study and meta-analysis of phytosterols identifies a novel locus for serum levels of campesterol.
المؤلفون: 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.
المصدر: Human genomics [Hum Genomics] 2024 Aug 01; Vol. 18 (1), pp. 85. Date of Electronic Publication: 2024 Aug 01.
نوع المنشور: Journal Article; Meta-Analysis
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101202210 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-7364 (Electronic) Linking ISSN: 14739542 NLM ISO Abbreviation: Hum Genomics Subsets: MEDLINE
أسماء مطبوعة: Publication: 2012- : London : BioMed Central
Original Publication: London : Henry Stewart Publications, c2003-
مواضيع طبية MeSH: Genome-Wide Association Study* , Phytosterols*/blood , Phytosterols*/genetics , Phytosterols*/adverse effects , Polymorphism, Single Nucleotide*/genetics , Sitosterols*/blood , Lipid Metabolism, Inborn Errors*/genetics , Lipid Metabolism, Inborn Errors*/blood , ATP Binding Cassette Transporter, Subfamily G, Member 5*/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 8*/genetics, Humans ; Male ; Female ; Intestinal Diseases/genetics ; Intestinal Diseases/blood ; Adult ; Cholesterol/blood ; Cholesterol/analogs & derivatives ; Hypercholesterolemia/genetics ; Hypercholesterolemia/blood ; Middle Aged ; Lipoproteins/blood ; Lipoproteins/genetics ; ATP-Binding Cassette Transporters/genetics
مستخلص: 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).)
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فهرسة مساهمة: Keywords: Genetic predispositions; Genome-wide association study; Meta-analysis; Middle Eastern; Polygenic risk score; Sitosterolemia
المشرفين على المادة: 0 (Phytosterols)
5L5O665639 (campesterol)
0 (Sitosterols)
5LI01C78DD (gamma-sitosterol)
0 (ATP Binding Cassette Transporter, Subfamily G, Member 5)
0 (ATP Binding Cassette Transporter, Subfamily G, Member 8)
0 (ABCG5 protein, human)
0 (ABCG8 protein, human)
97C5T2UQ7J (Cholesterol)
0 (Lipoproteins)
0 (ATP-Binding Cassette Transporters)
SCR Disease Name: Sitosterolemia
تواريخ الأحداث: Date Created: 20240801 Date Completed: 20240802 Latest Revision: 20240804
رمز التحديث: 20240804
مُعرف محوري في PubMed: PMC11295598
DOI: 10.1186/s40246-024-00649-x
PMID: 39090729
قاعدة البيانات: MEDLINE
الوصف
تدمد:1479-7364
DOI:10.1186/s40246-024-00649-x