Whole-genome sequence-based analysis of high-density lipoprotein cholesterol.

TitleWhole-genome sequence-based analysis of high-density lipoprotein cholesterol.
Publication TypeJournal Article
Year of Publication2013
AuthorsMorrison, AC, Voorman, A, Johnson, AD, Liu, X, Yu, J, Li, A, Muzny, DM, Yu, F, Rice, K, Zhu, C, Bis, J, Heiss, G, O'Donnell, CJ, Psaty, BM, L Cupples, A, Gibbs, RA, Boerwinkle, E
Corporate Authors
JournalNat Genet
Volume45
Issue8
Pagination899-901
Date Published2013 Aug
ISSN1546-1718
KeywordsCholesterol, HDL, Computational Biology, Databases, Genetic, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genomics, Heterozygote, Humans, Open Reading Frames
Abstract

We describe initial steps for interrogating whole-genome sequence data to characterize the genetic architecture of a complex trait, levels of high-density lipoprotein cholesterol (HDL-C). We report whole-genome sequencing and analysis of 962 individuals from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. From this analysis, we estimate that common variation contributes more to heritability of HDL-C levels than rare variation, and screening for mendelian variants for dyslipidemia identified individuals with extreme HDL-C levels. Whole-genome sequencing analyses highlight the value of regulatory and non-protein-coding regions of the genome in addition to protein-coding regions.

DOI10.1038/ng.2671
Alternate JournalNat. Genet.
PubMed ID23770607
PubMed Central IDPMC4030301
Grant ListAG-023629 / AG / NIA NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
AG-15928 / AG / NIA NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
R01 HL072810 / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
RC2HL102419-02 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States