Ancestry-driven metabolite variation provides insights into disease states in admixed populations.
Admixture mapping
Hispanics/Latino populations
Local ancestry
Metabolites
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
17 07 2023
17 07 2023
Historique:
received:
22
11
2022
accepted:
10
07
2023
medline:
19
7
2023
pubmed:
18
7
2023
entrez:
17
7
2023
Statut:
epublish
Résumé
Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
Sections du résumé
BACKGROUND
Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.
METHODS
We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.
RESULTS
By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.
CONCLUSIONS
Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
Identifiants
pubmed: 37461045
doi: 10.1186/s13073-023-01209-z
pii: 10.1186/s13073-023-01209-z
pmc: PMC10351197
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK117445
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65235
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65233
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD012765
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK130044
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65236
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65237
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65234
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Nat Commun. 2022 Aug 22;13(1):4923
pubmed: 35995766
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Commun Biol. 2021 Jul 28;4(1):918
pubmed: 34321601
Science. 2008 Feb 22;319(5866):1100-4
pubmed: 18292342
Am J Respir Crit Care Med. 2018 Jul 15;198(2):208-219
pubmed: 29394082
Prog Lipid Res. 2022 Apr;86:101165
pubmed: 35508275
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4166-4175
pubmed: 30782801
Physiol Rev. 2019 Oct 1;99(4):1819-1875
pubmed: 31434538
Genome Biol. 2022 Jan 7;23(1):13
pubmed: 34996498
Arterioscler Thromb Vasc Biol. 2019 May;39(5):869-875
pubmed: 30866658
Nature. 2014 Feb 6;506(7486):97-101
pubmed: 24390345
Nat Rev Genet. 2012 Nov;13(11):759-69
pubmed: 23032255
Genome Biol Evol. 2019 May 1;11(5):1417-1430
pubmed: 30942856
Am J Hum Genet. 2013 Aug 8;93(2):278-88
pubmed: 23910464
Am J Hum Genet. 2020 Mar 5;106(3):371-388
pubmed: 32142644
Nat Med. 2021 Mar;27(3):471-479
pubmed: 33707775
Am J Hum Genet. 2007 Nov;81(5):1084-97
pubmed: 17924348
PLoS Comput Biol. 2011 Dec;7(12):e1002325
pubmed: 22216000
Nat Genet. 2017 Apr;49(4):568-578
pubmed: 28263315
Ann Epidemiol. 2010 Aug;20(8):642-9
pubmed: 20609344
Nat Genet. 2014 Jun;46(6):543-550
pubmed: 24816252
Nat Commun. 2022 Jun 6;13(1):3124
pubmed: 35668104
Circ Cardiovasc Genet. 2013 Oct;6(5):505-13
pubmed: 24047826
Am J Hum Genet. 2020 Nov 5;107(5):849-863
pubmed: 33031748
Nat Commun. 2019 Jan 3;10(1):29
pubmed: 30604766
Science. 2016 Oct 7;354(6308):54-59
pubmed: 27846491
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Intractable Rare Dis Res. 2021 Nov;10(4):257-262
pubmed: 34877237
Elife. 2020 Dec 29;9:
pubmed: 33372659
Trends Genet. 2020 Jun;36(6):415-428
pubmed: 32396835
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Genes Nutr. 2013 Jan;8(1):19-27
pubmed: 23065485
Am J Hum Genet. 2016 Jan 7;98(1):165-84
pubmed: 26748518
Cell Metab. 2017 Jan 10;25(1):43-56
pubmed: 28094011
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
PLoS Genet. 2008 Nov;4(11):e1000282
pubmed: 19043545
Bioinformatics. 2019 Dec 15;35(24):5346-5348
pubmed: 31329242
Nature. 2015 Dec 24;528(7583):499-503
pubmed: 26595274
Genet Epidemiol. 2010 Sep;34(6):591-602
pubmed: 20718045
Nucleic Acids Res. 2017 Jan 4;45(D1):D896-D901
pubmed: 27899670
J Am Soc Nephrol. 2017 Jul;28(7):2211-2220
pubmed: 28137830
Front Nutr. 2022 Feb 08;8:808054
pubmed: 35211495
J Lipid Res. 2020 Dec;61(12):1539-1555
pubmed: 33037133
J Am Soc Nephrol. 2017 Mar;28(3):915-922
pubmed: 27650483
J Clin Invest. 2018 Jul 2;128(7):2657-2669
pubmed: 29757195
Curr Diab Rep. 2014 Feb;14(2):455
pubmed: 24445905
Hum Mol Genet. 2019 Jul 1;28(13):2212-2223
pubmed: 31220269
PLoS One. 2017 Nov 20;12(11):e0188400
pubmed: 29155883
Am J Hum Genet. 2022 Jun 2;109(6):1038-1054
pubmed: 35568032
Mol Biol Evol. 2022 Apr 11;39(4):
pubmed: 35460423
J Proteome Res. 2021 Nov 5;20(11):5103-5114
pubmed: 34699229
Ann Epidemiol. 2010 Aug;20(8):629-41
pubmed: 20609343
Metabolites. 2021 Jan 14;11(1):
pubmed: 33466750
Curr Hypertens Rep. 2013 Apr;15(2):108-13
pubmed: 23397215
JCI Insight. 2018 Nov 2;3(21):
pubmed: 30385718
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2195-2199
pubmed: 28193867
Hum Mol Genet. 2019 Feb 15;28(4):675-687
pubmed: 30403821
J Am Soc Nephrol. 2022 Jan;33(1):77-87
pubmed: 34670813
G3 (Bethesda). 2016 Jun 01;6(6):1525-34
pubmed: 27172203