Genome-wide association study and meta-analysis of phytosterols identifies a novel locus for serum levels of campesterol.
Humans
Genome-Wide Association Study
Phytosterols
/ blood
Polymorphism, Single Nucleotide
/ genetics
Sitosterols
/ blood
Lipid Metabolism, Inborn Errors
/ genetics
ATP Binding Cassette Transporter, Subfamily G, Member 5
/ genetics
ATP Binding Cassette Transporter, Subfamily G, Member 8
/ genetics
Male
Female
Intestinal Diseases
/ genetics
Adult
Cholesterol
/ blood
Hypercholesterolemia
/ genetics
Middle Aged
Lipoproteins
/ blood
ATP-Binding Cassette Transporters
/ genetics
Genetic predispositions
Genome-wide association study
Meta-analysis
Middle Eastern
Polygenic risk score
Sitosterolemia
Journal
Human genomics
ISSN: 1479-7364
Titre abrégé: Hum Genomics
Pays: England
ID NLM: 101202210
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
received:
15
03
2024
accepted:
22
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
1
8
2024
Statut:
epublish
Résumé
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
Identifiants
pubmed: 39090729
doi: 10.1186/s40246-024-00649-x
pii: 10.1186/s40246-024-00649-x
doi:
Substances chimiques
Phytosterols
0
campesterol
5L5O665639
Sitosterols
0
gamma-sitosterol
5LI01C78DD
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
0
Cholesterol
97C5T2UQ7J
Lipoproteins
0
ATP-Binding Cassette Transporters
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
85Informations de copyright
© 2024. The Author(s).
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