Scholars@Duke

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Publication ,  Journal Article
Zekavat, SM; Ruotsalainen, S; Handsaker, RE; Alver, M; Bloom, J; Poterba, T; Seed, C; Ernst, J; Chaffin, M; Engreitz, J; Peloso, GM; Yang, C ...
Published in: Nat Commun
July 4, 2018
Published version (DOI) Link to item

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

Duke Scholars

Marilyn Jo Telen
Author Marilyn Jo Telen Medicine, Hematology
Allison Elizabeth Ashley-Koch
Author Allison Elizabeth Ashley-Koch Medicine, Nephrology
Yongmei Liu
Author Yongmei Liu Medicine, Cardiology
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Published In

Nat Commun

DOI

10.1038/s41467-018-04668-w

EISSN

2041-1723

Publication Date

July 4, 2018

Volume

9

Issue

1

Start / End Page

2606

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Lipoprotein(a)
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Gene Expression
 

Citation

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Zekavat, S. M., Ruotsalainen, S., Handsaker, R. E., Alver, M., Bloom, J., Poterba, T., … NHLBI TOPMed Lipids Working Group. (2018). Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. Nat Commun, 9(1), 2606. https://doi.org/10.1038/s41467-018-04668-w
Zekavat, Seyedeh M., Sanni Ruotsalainen, Robert E. Handsaker, Maris Alver, Jonathan Bloom, Timothy Poterba, Cotton Seed, et al. “Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.” Nat Commun 9, no. 1 (July 4, 2018): 2606. https://doi.org/10.1038/s41467-018-04668-w.
Zekavat SM, Ruotsalainen S, Handsaker RE, Alver M, Bloom J, Poterba T, et al. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. Nat Commun. 2018 Jul 4;9(1):2606.
Zekavat, Seyedeh M., et al. “Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.” Nat Commun, vol. 9, no. 1, July 2018, p. 2606. Pubmed, doi:10.1038/s41467-018-04668-w.
Zekavat SM, Ruotsalainen S, Handsaker RE, Alver M, Bloom J, Poterba T, Seed C, Ernst J, Chaffin M, Engreitz J, Peloso GM, Manichaikul A, Yang C, Ryan KA, Fu M, Johnson WC, Tsai M, Budoff M, Vasan RS, Cupples LA, Rotter JI, Rich SS, Post W, Mitchell BD, Correa A, Metspalu A, Wilson JG, Salomaa V, Kellis M, Daly MJ, Neale BM, McCarroll S, Surakka I, Esko T, Ganna A, Ripatti S, Kathiresan S, Natarajan P, NHLBI TOPMed Lipids Working Group. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. Nat Commun. 2018 Jul 4;9(1):2606.

Published In

Nat Commun

DOI

10.1038/s41467-018-04668-w

EISSN

2041-1723

Publication Date

July 4, 2018

Volume

9

Issue

1

Start / End Page

2606

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • White People
  • Risk Factors
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Lipoprotein(a)
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Gene Expression