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oai:repisalud.isciii.es:20.500.12105/75122025-05-13T11:15:59Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Geng, Xin author Irvin, Marguerite R author Hidalgo, Bertha author Aslibekyan, Stella author Srinivasasainagendra, Vinodh author An, Ping author Frazier-Wood, Alexis C author Tiwari, Hemant K author Dave, Tushar author Ryan, Kathleen author Ordovas, Jose M author Straka, Robert J author Feitosa, Mary F author Hopkins, Paul N author Borecki, Ingrid author Province, Michael A author Mitchell, Braxton D author Arnett, Donna K author Zhi, Degui author 2019 Background: Associations of both common and rare genetic variants with fasting blood lipids have been extensively studied. However, most of the rare coding variants associated with lipids are population-specific, and exploration of genetic data from diverse population samples may enhance the identification of novel associations with rare variants. Results: We searched for novel coding genetic variants associated with fasting lipid levels in 894 samples from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) with exome-wide sequencing-based genotype data. In single variant tests, one variant (rs11171663 in ITGA7) was associated with fasting triglyceride levels (P = 7.66E-08), explaining approximately 3.2% of the total trait variance. In gene-based tests, we found statistically significant associations between ITGA7 (P = 1.77E-07) and SLCO2A1 (P = 7.18E-07) and triglycerides, as well as between POT1 (P = 3.00E-07) and low-density lipoprotein cholesterol. In another independent replication cohort consisting of 3,183 African American samples from Hypertension Genetic Epidemiology Network (HyperGEN) and the Genetic Epidemiology Network of Arteriopathy (GENOA), the top genes achieved P-values of 0.04 (ITGA7), 0.08 (SLCO2A1), and 0.02 (POT1). In GOLDN, gene transcript levels of ITGA7 and SLCO2A1 were associated with fasting triglycerides (P = 0.07 and P = 0.02), highlighting functional relevance of our findings. Conclusion: In this study, we present preliminary evidence of novel rare variant determinants of fasting lipids, and reveal potential underlying molecular mechanisms. Moreover, these results were replicated in an independent cohort. Our findings may inform novel biomarkers of disease risk and treatment targets. Front Genet. 2019; 10:158 10.3389/fgene.2019.00158 1664-8021 Frontiers in genetics 30863429 http://hdl.handle.net/20.500.12105/7512 HDL LDL Cholesterol Epidemiology Genetics Rare variant Triglyceride Whole exome sequencing An Exome-Wide Sequencing Study of the GOLDN Cohort Reveals Novel Associations of Coding Variants and Fasting Plasma Lipids