Title | Identification of Genetic Variants Linking Protein C and Lipoprotein Metabolism: The ARIC Study (Atherosclerosis Risk in Communities). |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Pankow JS, Tang W, Pankratz N, Guan W, Weng L-C, Cushman M, Boerwinkle E |
Secondary Authors | Folsom AR |
Journal | Arterioscler Thromb Vasc Biol |
Volume | 37 |
Issue | 3 |
Pagination | 589-597 |
Date Published | 2017 03 |
ISSN | 1524-4636 |
Keywords | Adaptor Proteins, Vesicular Transport, African Americans, Atherosclerosis, Cadherins, Cholesterol, LDL, Chromosomes, Human, Pair 1, European Continental Ancestry Group, Female, Gene Expression Profiling, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Hemostasis, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Oligonucleotide Array Sequence Analysis, Phenotype, Phosphoproteins, Polymorphism, Single Nucleotide, Protein C, Risk Factors, Triglycerides, United States |
Abstract | OBJECTIVE: Previous studies have identified common genetic variants in 4 chromosomal regions that together account for 14% to 15% of the variance in circulating levels of protein C. To further characterize the genetic architecture of protein C, we obtained denser coverage at some loci, extended investigation of protein C to low-frequency and rare variants, and searched for new associations in genes known to influence protein C. APPROACH AND RESULTS: Genetic associations with protein C antigen level were evaluated in ≤10 778 European and 3190 black participants aged 45 to 64 years. Analyses included >26 million autosomal variants available after imputation to the 1000 Genomes reference panel along with additional low-frequency and rare variants directly genotyped using the Illumina ITMAT-Broad-CARe chip and Illumina HumanExome BeadChip. Genome-wide significant associations ( CONCLUSIONS: Discovery of variants influencing circulating protein C levels in the CELSR2-PSRC1-SORT1 region may indicate a novel genetic link between lipoprotein metabolism and hemostasis. |
DOI | 10.1161/ATVBAHA.116.308109 |
Alternate Journal | Arterioscler Thromb Vasc Biol |
PubMed ID | 28082259 |
PubMed Central ID | PMC5376064 |
Grant List | HHSN268201100012C / HL / NHLBI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States R01 HL095603 / HL / NHLBI NIH HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States N01 HC065226 / HC / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States |