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Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

ABSTRACT: Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many genetic variants associated with blood lipid traits have been identified in Europeans, similar data in Middle Eastern populations are limited. We performed a genome-wide association study with Arab individuals (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify possible associations of genetic variants with high lipid levels. We used Illumina HumanOmniExpress BeadChip and candidate SNP genotyping in the discovery and replication phases, respectively. For association tests, we used genetic models that were based on additive and recessive modes of inheritance. High triglycerides (TGs) were recessively associated with six risk variants (rs1002487/RPS6KA1, rs11805972/LAD1) rs7761746/Or5v1, rs39745/CTTNBP2-LSM8, rs2934952/PGAP3, and rs9626773/RP11-191L9.4-CERK) at genome-wide significance (P ? 6.12E-09), and another six variants (rs10873925/ST6GALNAC5, rs4663379/SPP2-ARL4C, rs10033119/NPY1R, rs17709449/LINC00911-FLRT2, rs11654954/CDK12-NEUROD2, and rs9972882/STARD3) were associated at borderline significance (P ? 5.0E-08). High TG was also additively associated with rs11654954. All of the 12 identified markers are novel and are harbored in runs of homozygosity. Literature evidence supports the involvement of these gene loci in lipid-related processes. This study in an Arab population augments international efforts to identify genetic regulation of lipid traits.

SUBMITTER: Hebbar P

PROVIDER: S-EPMC6168314 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

Hebbar Prashantha P Nizam Rasheeba R Melhem Motasem M Alkayal Fadi F Elkum Naser N John Sumi Elsa SE Tuomilehto Jaakko J Alsmadi Osama O Thanaraj Thangavel Alphonse TA

Journal of lipid research 20180814 10

Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many genetic variants associated with blood lipid traits have been identified in Europeans, similar data in Middle Eastern populations are limited. We performed a genome-wide association study with Arab individuals (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify possible associations of genetic variants with high lipid levels. We used Illumina HumanOmniExpress BeadChip and c ...[more]

PMID: 30108155

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Project description:BackgroundOvine footrot caused by Dichelobacter nodosus (D. nodosus) is a contagious disease with serious economic and welfare impacts in sheep production systems worldwide. A better understanding of the host genetic architecture regarding footrot resistance/susceptibility is crucial to develop disease control strategies that efficiently reduce infection and its severity. A genome-wide association study was performed using a customized SNP array (47,779 SNPs in total) to identify genetic variants associated to footrot resistance/susceptibility in two Portuguese native breeds, i.e. Merino Branco and Merino Preto, and a population of crossbred animals. A cohort of 1375 sheep sampled across 17 flocks, located in the Alentejo region (southern Portugal), was included in the analyses.ResultsPhenotypes were scored from 0 (healthy) to 5 (severe footrot) based on visual inspection of feet lesions, following the Modified Egerton System. Using a linear mixed model approach, three SNPs located on chromosome 24 reached genome-wide significance after a Bonferroni correction (p < 0.05). Additionally, six genome-wide suggestive SNPs were identified each on chromosomes 2, 4, 7, 8, 9 and 15. The annotation and KEGG pathway analyses showed that these SNPs are located within regions of candidate genes such as the nonsense mediated mRNA decay associated PI3K related kinase (SMG1) (chromosome 24) and the RALY RNA binding protein like (RALYL) (chromosome 9), both involved in immunity, and the heparan sulfate proteoglycan 2 (HSPG2) (chromosome 2) and the Thrombospodin 1 (THBS1) (chromosome 7) implicated in tissue repair and wound healing processes.ConclusionThis is the first attempt to identify molecular markers associated with footrot in Portuguese Merino sheep. These findings provide relevant information on a likely genetic association underlying footrot resistance/susceptibility and the potential candidate genes affecting this trait. Genetic selection strategies assisted on the information obtained from this study could enhance Merino sheep-breeding programs, in combination with farm management strategies, for a more effective and sustainable long-term solution for footrot control.

Project description:Background:Rates of asthma in Jordan have been doubled in the past decade, but this increased prevalence was not met with improved asthma control protocols. The aim of the present study was to assess whether there was any significant association between the level of asthma control and certain single-nucleotide polymorphisms (SNPs) in five genes: (ADRB2; rs1042713 and rs1042714), (CRHR1; rs1876828, rs242939, and rs242941), (STIP1; rs2236647), (ADH5, rs1154400), and (ARG1; rs2781659). These SNPs were selected based on their involvement in enzymes and receptors that are related to asthma pathways and subsequent response to medication and based on a high degree of linkage disequilibrium. Patients and methods:A cross-sectional genetic association study was conducted from June 2016 to June 2017 in the two major hospitals in Jordan. The present study involved sampling from adult asthmatic patients of Arab descent who were selected from two phenotypic groups, ie, controlled and uncontrolled asthma. The blood samples and medical data were collected from the participants. DNA samples were extracted, quantified, and genotyped according to standard operating procedure. Allelic and haplotypic analyses were performed using the Haploview®. Results:A total of 245 Arab asthmatic patients were enrolled in this study. Genotyping analysis revealed that the two SNPs (rs1042713 and rs1042714) in ADRB2 gene, along with their related haplotypes, were nominally significantly associated with asthma control in the Jordanian population. The A-allele of rs1042713 and the C-allele of rs1042714 were more common in the uncontrolled asthma group than in the controlled asthma group (P=0.048 and P=0.017, respectively). Conclusion:This was the first study that identified the nominal significant association between the level of asthma control and genetic variants in ADRB2 gene in Arab population. Further studies in other Arab region with larger sample size are recommended to confirm the relationship.

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Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

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Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

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