Genome-wide association study of blood lipids in Indians confirms universality of established variants

Bandesh, Khushdeep; Prasad, Gauri; Giri, Anil; Kauser, Yasmeen; Upadhyay, Medha; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

doi:10.1038/s10038-019-0591-7

Cited by 27 publications

(22 citation statements)

References 53 publications

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“…Several genome wide association studies (GWAS) have been performed with the aim of searching for new genes involved in cholesterol metabolism [28][29][30]. However, none of these studies has demonstrated an association between genetic variants in STAP1 and cholesterol levels.…”

Section: Discussionmentioning

confidence: 99%

Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia

et al. 2020

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“…DNA samples were genotyped genome-wide using Illumina Human610-Quad Beadchips (Illumina Inc., San Diego, CA, USA) as part of GWAS studies conducted for T2D and interrelated quantitative metabolic phenotypes earlier in our laboratory [14,15,27,36,37,38]. The GenCall algorithm employed in GenomeStudio software (Illumina, Inc., San Diego, CA, USA) was used to compute genotype calls.…”

Section: Methodsmentioning

confidence: 99%

“…The genetic heritability is liable up to 50% for some individual metabolic components and 13–30% for collective MetS phenotype [9,10,11,12]. Several large-scale genetic studies have been performed to identify MetS related single nucleotide polymorphisms (SNPs) considering independent components of MetS as a quantitative trait [13,14,15,16,17]. In view of MetS as a binary phenotype, several other genome-wide studies worldwide identified numerous loci influencing the combined metabolic syndrome outcome.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians

et al. 2019

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Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (N = 2158) and replication phase (N = 7935). We discovered two variants within/near the CETP gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional CETP loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the CETP locus constituting all seven CETP signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of SFRP1 gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome.

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“…MetS heritability has been reported between 13% and 30% and for some individual metabolic components can be as high as 50% [ 4 , 5 , 6 ]. Several Genome-wide association studies (GWAS) have been performed to identify MetS-related single nucleotide polymorphisms (SNPs) considering independent components of MetS as quantitative traits [ 7 , 8 , 9 ]. In view of MetS as a binary phenotype, several GWAS have identified numerous loci influencing its presence.…”

Section: Introductionmentioning

confidence: 99%

The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population

León-Reyes

Rivera‐Paredez

Fernández-López

et al. 2020

Genes

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The Mexican population has one of the highest prevalences of metabolic syndrome (MetS) worldwide. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) with MetS and its components. First, we performed a pilot Genome-wide association study (GWAS) scan on a sub-sample derived from the Health Workers Cohort Study (HWCS) (n = 411). Based on GWAS results, we selected the rs1784042 and rs17120425 SNPs in the SIDT1 transmembrane family member 2 (SIDT2) gene for replication in the entire cohort (n = 1963), using predesigned TaqMan assays. We observed a prevalence of MetS in the HWCS of 52.6%. The minor allele frequency for the variant rs17120425 was 10% and 29% for the rs1784042. The SNP rs1784042 showed an overall association with MetS (OR = 0.82, p = 0.01) and with low levels of high-density lipoprotein (HDL-c) (odds ratio (OR) = 0.77, p = 0.001). The SNP rs17120425 had a significant association with type 2 diabetes (T2D) risk in the overall population (OR = 1.39, p = 0.033). Our results suggest an association of the rs1784042 and rs17120425 variants with MetS, through different mechanisms in the Mexican population. Further studies in larger samples and other populations are required to validate these findings and the relevance of these SNPs in MetS.

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Genome-wide association study of blood lipids in Indians confirms universality of established variants

Cited by 27 publications

References 53 publications

Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia

Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia

Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians

The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population

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