An Amish founder population reveals rare-population genetic determinants of the human lipidome.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
received:
27
08
2021
accepted:
17
03
2022
entrez:
8
4
2022
pubmed:
9
4
2022
medline:
12
4
2022
Statut:
epublish
Résumé
Identifying the genetic determinants of inter-individual variation in lipid species (lipidome) may provide deeper understanding and additional insight into the mechanistic effect of complex lipidomic pathways in CVD risk and progression beyond simple traditional lipids. Previous studies have been largely population based and thus only powered to discover associations with common genetic variants. Founder populations represent a powerful resource to accelerate discovery of previously unknown biology associated with rare population alleles that have risen to higher frequency due to genetic drift. We performed a genome-wide association scan of 355 lipid species in 650 individuals from the Amish founder population including 127 lipid species not previously tested. To the best of our knowledge, we report for the first time the lipid species associated with two rare-population but Amish-enriched lipid variants: APOB_rs5742904 and APOC3_rs76353203. We also identified novel associations for 3 rare-population Amish-enriched loci with several sphingolipids and with proposed potential functional/causal variant in each locus including GLTPD2_rs536055318, CERS5_rs771033566, and AKNA_rs531892793. We replicated 7 previously known common loci including novel associations with two sterols: androstenediol with UGT locus and estriol with SLC22A8/A24 locus. Our results show the double power of founder populations and detailed lipidome to discover novel trait-associated variants.
Identifiants
pubmed: 35393526
doi: 10.1038/s42003-022-03291-2
pii: 10.1038/s42003-022-03291-2
pmc: PMC8989972
doi:
Substances chimiques
AKNA protein, human
0
DNA-Binding Proteins
0
Lipids
0
Nuclear Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
334Subventions
Organisme : NHGRI NIH HHS
ID : T32 HG008341
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL091357
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL137181
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL084756
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL072524
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL072515
Pays : United States
Informations de copyright
© 2022. The Author(s).
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