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

Prashantha Hebbar, Rasheeba Nizam, Motasem  Melhem, Fadi Alkayal, Naser Elkum, Sumi Elsa John, Jaakko Tuomilehto, Osama Alsmadi, Alphonse Thangavel Thanaraj

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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 reces-sively 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.

Original languageEnglish
Pages (from-to)1951-1966
Number of pages16
JournalJournal of Lipid Research
Volume59
Issue number10
DOIs
Publication statusPublished - 1 Jan 2018

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Keywords

  • Diabetes
  • Genetics
  • Genomics
  • High density lipoprotein
  • Lipid
  • Lipoprotein metabolism
  • Obesity
  • Triglycerides

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