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Whole genome sequence analysis of blood lipid levels in >66,000 individuals.

Publication ,  Journal Article
Selvaraj, MS; Li, X; Li, Z; Pampana, A; Zhang, DY; Park, J; Aslibekyan, S; Bis, JC; Brody, JA; Cade, BE; Chuang, L-M; Chung, R-H; Curran, JE ...
Published in: Nat Commun
October 11, 2022
Published version (DOI) Open Access Copy (Duke) Link to item

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

Duke Scholars

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

Nat Commun

DOI

10.1038/s41467-022-33510-7

EISSN

2041-1723

Publication Date

October 11, 2022

Volume

13

Issue

1

Start / End Page

5995

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Lipids
  • Humans
  • Genome-Wide Association Study
  • Cholesterol, LDL
  • Alleles
 

Citation

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Selvaraj, M. S., Li, X., Li, Z., Pampana, A., Zhang, D. Y., Park, J., … Natarajan, P. (2022). Whole genome sequence analysis of blood lipid levels in >66,000 individuals. Nat Commun, 13(1), 5995. https://doi.org/10.1038/s41467-022-33510-7
Selvaraj, Margaret Sunitha, Xihao Li, Zilin Li, Akhil Pampana, David Y. Zhang, Joseph Park, Stella Aslibekyan, et al. “Whole genome sequence analysis of blood lipid levels in >66,000 individuals.” Nat Commun 13, no. 1 (October 11, 2022): 5995. https://doi.org/10.1038/s41467-022-33510-7.
Selvaraj MS, Li X, Li Z, Pampana A, Zhang DY, Park J, et al. Whole genome sequence analysis of blood lipid levels in >66,000 individuals. Nat Commun. 2022 Oct 11;13(1):5995.
Selvaraj, Margaret Sunitha, et al. “Whole genome sequence analysis of blood lipid levels in >66,000 individuals.” Nat Commun, vol. 13, no. 1, Oct. 2022, p. 5995. Pubmed, doi:10.1038/s41467-022-33510-7.
Selvaraj MS, Li X, Li Z, Pampana A, Zhang DY, Park J, Aslibekyan S, Bis JC, Brody JA, Cade BE, Chuang L-M, Chung R-H, Curran JE, de las Fuentes L, de Vries PS, Duggirala R, Freedman BI, Graff M, Guo X, Heard-Costa N, Hidalgo B, Hwu C-M, Irvin MR, Kelly TN, Kral BG, Lange L, Lisa M, Lubitz SA, Manichaikul AW, Michael P, Montasser ME, Morrison AC, Naseri T, O’Connell JR, Palmer ND, Peyser PA, Reupena MS, Smith JA, Sun X, Taylor KD, Tracy RP, Tsai MY, Wang Z, Wang Y, Bao W, Wilkins JT, Yanek LR, Zhao W, Arnett DK, Blangero J, Boerwinkle E, Bowden DW, Chen Y-DI, Correa A, Cupples LA, Dutcher SK, Ellinor PT, Fornage M, Gabriel S, Germer S, Gibbs R, He J, Kaplan RC, Kardia SLR, Kim R, Kooperberg C, Loos RJF, Viaud-Martinez KA, Mathias RA, McGarvey ST, Mitchell BD, Nickerson D, North KE, Psaty BM, Redline S, Reiner AP, Vasan RS, Rich SS, Willer C, Rotter JI, Rader DJ, Lin X, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Peloso GM, Natarajan P. Whole genome sequence analysis of blood lipid levels in >66,000 individuals. Nat Commun. 2022 Oct 11;13(1):5995.

Published In

Nat Commun

DOI

10.1038/s41467-022-33510-7

EISSN

2041-1723

Publication Date

October 11, 2022

Volume

13

Issue

1

Start / End Page

5995

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Lipids
  • Humans
  • Genome-Wide Association Study
  • Cholesterol, LDL
  • Alleles