Austin Health

Title
Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.
Publication Date
2022-06-06
Author(s)
Cadby, Gemma
Giles, Corey
Melton, Phillip E
Huynh, Kevin
Mellett, Natalie A
Duong, Thy
Nguyen, Anh
Cinel, Michelle
Smith, Alex
Olshansky, Gavriel
Wang, Tingting
Brozynska, Marta
Inouye, Mike
McCarthy, Nina S
Ariff, Amir
Hung, Joseph
Hui, Jennie
Beilby, John
Dubé, Marie-Pierre
Watts, Gerald F
Shah, Sonia
Wray, Naomi R
Lim, Wei Ling Florence
Chatterjee, Pratishtha
Martins, Ian
Laws, Simon M
Porter, Tenielle
Vacher, Michael
Bush, Ashley I
Rowe, Christopher C
Villemagne, Victor L
Ames, David
Masters, Colin L
Taddei, Kevin
Arnold, Matthias
Kastenmüller, Gabi
Nho, Kwangsik
Saykin, Andrew J
Han, Xianlin
Kaddurah-Daouk, Rima
Martins, Ralph N
Blangero, John
Meikle, Peter J
Moses, Eric K
Type of document
Journal Article
OrcId
http://orcid.org/0000-0001-7317-6531
http://orcid.org/0000-0002-6050-1259
http://orcid.org/0000-0003-4026-2964
http://orcid.org/0000-0001-6170-2207
http://orcid.org/0000-0002-2521-078X
http://orcid.org/0000-0002-5122-5547
http://orcid.org/0000-0002-4468-6097
http://orcid.org/0000-0001-5860-4526
http://orcid.org/0000-0001-7421-3357
http://orcid.org/0000-0002-8988-2147
http://orcid.org/0000-0003-4877-1958
http://orcid.org/0000-0002-2390-1501
http://orcid.org/0000-0002-4355-7082
http://orcid.org/0000-0001-8259-9069
http://orcid.org/0000-0002-4666-0923
http://orcid.org/0000-0002-2368-7322
http://orcid.org/0000-0002-1376-8532
http://orcid.org/0000-0002-8615-2413
http://orcid.org/0000-0003-1858-5732
http://orcid.org/0000-0001-6250-5723
http://orcid.org/0000-0002-2593-4665
http://orcid.org/0000-0001-7781-4465
http://orcid.org/0000-0001-8259-9069
http://orcid.org/0000-0003-3910-2453
http://orcid.org/0000-0002-5832-9875
http://orcid.org/0000-0003-3072-7940
DOI
10.1038/s41467-022-30875-7
Abstract
We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
Link
Citation
Nature communications 2022; 13(1): 3124
Jornal Title
Nature communications

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