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Identification of Genetic Variants Linking Protein C and Lipoprotein Metabolism: The ARIC Study (Atherosclerosis Risk in Communities).

TitleIdentification of Genetic Variants Linking Protein C and Lipoprotein Metabolism: The ARIC Study (Atherosclerosis Risk in Communities).
Publication TypeJournal Article
Year of Publication2017
AuthorsPankow JS, Tang W, Pankratz N, Guan W, Weng L-C, Cushman M, Boerwinkle E
Secondary AuthorsFolsom AR
JournalArterioscler Thromb Vasc Biol
Volume37
Issue3
Pagination589-597
Date Published2017 03
ISSN1524-4636
KeywordsAdaptor 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.

DOI10.1161/ATVBAHA.116.308109
Alternate JournalArterioscler Thromb Vasc Biol
PubMed ID28082259
PubMed Central IDPMC5376064
Grant ListHHSN268201100012C / 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