TY - JOUR
T1 - Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population
AU - Hebbar, Prashantha
AU - Nizam, Rasheeba
AU - Melhem, Motasem
AU - Alkayal, Fadi
AU - Elkum, Naser
AU - John, Sumi Elsa
AU - Tuomilehto, Jaakko
AU - Alsmadi, Osama
AU - Thanaraj, Alphonse Thangavel
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Diabetes
KW - Genetics
KW - Genomics
KW - High density lipoprotein
KW - Lipid
KW - Lipoprotein metabolism
KW - Obesity
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=85054086687&partnerID=8YFLogxK
U2 - 10.1194/jlr.P080218
DO - 10.1194/jlr.P080218
M3 - Article
C2 - 30108155
AN - SCOPUS:85054086687
VL - 59
SP - 1951
EP - 1966
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 10
ER -