title: A common variant association study reveals novel susceptibility loci for low HDL-cholesterol levels in ethnic Arabs.
abstract: The genetic susceptibility to acquiring low high density lipoprotein-cholesterol (LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high-density Axiom Genome-Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations (SNPs) to genotype 5495 individuals in a two-phase study involving discovery and validation sets of experiments. The rs1800775 [1.31 (1.22-1.42); p = 3.41E-12] in the CETP gene and rs359027 [1.26 (1.16-1.36); p = 2.55E-08] in the LMCD1 gene were significantly associated with LHDLC levels. Furthermore, rs3104435 [1.26 (1.15-1.38); p = 1.19E-06] at the MATN1 locus, rs9835344 [1.16 (1.08-1.26); p = 8.75E-06] in the CNTN6 gene, rs1559997 [1.3 (1.14-1.47); p = 9.48E-06] in the SDS gene and rs1670273 [1.2 (1.1-1.31); p = 4.81E-06] in the DMN/SYNM gene exhibited suggestive association with the disorder. Seven other variants including rs1147169 in the PLCL1 gene, rs10248618 in the DNAH11, rs476155 in the GLIS3, rs7024300 in the ABCA1, intergenic rs10836699, rs11603691 in P2RX3 and rs750134 in CORO1C gene exhibited borderline protective properties. Validation and joint meta-analysis resulted in rs1800775, rs3104435 and rs359027 retaining their predisposing properties, while rs10836699 and rs11603691 showed protective properties. Our data show several predisposing variants across the genome for LHDLC levels in ethnic Arabs.
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: S M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Western Australian Institute for Medical Research, University of Western Australia, Perth, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Ram
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: N P
authors.initials: NP
authors.lastname: Muiya
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: E
authors.initials: E
authors.lastname: Andres
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: N
authors.initials: N
authors.lastname: Mazhar
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Hagos
authors.affiliation: King Faisal Heart Institute, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Alshahid
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: B F
authors.initials: BF
authors.lastname: Meyer
authors.affiliation: Western Australian Institute for Medical Research, University of Western Australia, Perth, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Morahan
authors.affiliation: Genetics Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: N
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D018912:Arabs / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D056970:Co-Repressor Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D056970:Co-Repressor Proteins; D060588:LIM Domain Proteins; C406239:LMCD1 protein, human
keywords: CETP; DNAH11; LMCD1; common variants association study; ethnic Arabs; low HDL-cholesterol; meta-analysis