The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies DOI Creative Commons
Lauren E Louck, Kelly Copeland Cara, Kevin C. Klatt

et al.

Advances in Nutrition, Journal Year: 2023, Volume and Issue: 15(2), P. 100164 - 100164

Published: Dec. 20, 2023

Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new requirements, their link to disease endpoints. We conducted a scoping review studies assessing the association polymorphisms on choline-related metabolite concentrations subsequent associations with health outcomes. This study follows Preferred Reporting Items Systematic Reviews Meta-Analyses statement extension. Literature was searched September 28, 2022, in 4 databases: Embase, MEDLINE, Web Science, Biological Science Index. Studies any duration humans were considered. Any genome-wide (GWAS) investigating variant and/or Mendelian randomization (MR) genetically predicted outcome Qualitative evidence presented summary tables. From 1248 total reviewed articles, 53 included (GWAS = 27; MR 26). Forty-two tested variants GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, phosphatidylcholines. investigated between 52 unique 66 Of these, 47 significant reported 16 (primarily choline, phosphatidylcholines, sphingomyelins) 27 outcomes including cancer, cardiovascular, metabolic, bone, brain-related Some articles multiple types same outcome. Genetically are associated wide variety Further research needed assess how variability influences metabolism whether individuals lower would benefit from dietary intervention or supplementation.

Language: Английский

Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases DOI
Yiheng Chen, Tianyuan Lu, U. Pettersson

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(1), P. 44 - 53

Published: Jan. 1, 2023

Language: Английский

Citations

483
A reference map of potential determinants for the human serum metabolome DOI

Noam Bar,

Tal Korem, Omer Weissbrod

et al.

Nature, Journal Year: 2020, Volume and Issue: 588(7836), P. 135 - 140

Published: Nov. 11, 2020

Language: Английский

Citations

345
Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci DOI Creative Commons
Xianyong Yin, Lap Sum Chan, Debraj Bose

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 28, 2022

Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given multiple bottlenecks and expansions that shaped its history, enrichment many otherwise alleles has resulted. Here, we report genetic associations 1391 6136 men from late-settlement region Finland. We identify 303 novel association signals, more than one third at or enriched Finns. Many these signals genes not previously implicated metabolite genome-wide suggest mechanisms diseases disease-related traits.

Language: Английский

Citations

128
Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine DOI Creative Commons
Pascal Schlosser, Nora Scherer, Franziska Grundner-Culemann

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(6), P. 995 - 1008

Published: June 1, 2023

Abstract The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies paired metabolomes may identify underlying processes. We conducted genome-wide 1,916 metabolites detected 1,299 significant associations. Associations with 40% implicated would have been missed studying alone. urine-specific findings that provide information about metabolite reabsorption in kidney, such as aquaporin (AQP)-7-mediated glycerol transport, different metabolomic footprints kidney-expressed proteins are consistent their localization function, including transporters NaDC3 ( SLC13A3 ) ASBT SLC10A2 ). Shared genetic determinants 7,073 metabolite–disease combinations represent a resource to better understand metabolic diseases revealed connections dipeptidase 1 circulating digestive enzymes hypertension. Extending metabolome beyond yields unique insights into processes body compartments.

Language: Английский

Citations

47
Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits DOI Creative Commons
Ruidong Xiang, Irene van den Berg,

Iona M. MacLeod

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(39), P. 19398 - 19408

Published: Sept. 9, 2019

Many genome variants shaping mammalian phenotype are hypothesized to regulate gene transcription and/or be under selection. However, most of the evidence support this hypothesis comes from human studies. Systematic for regulatory and evolutionary signals contributing complex traits in a different model is needed. Sequence associated with expression (expression quantitative trait loci [eQTLs]) concentration metabolites (metabolic [mQTLs]) histone-modification marks several tissues were discovered multiomics data over 400 cattle. Variants selection constraint identified using databases multiple species. These analyses defined 30 sets variants, each set, we estimated genetic variance set explained across 34 11,923 bulls 32,347 cows 17,669,372 imputed variants. The per-variant heritability these was highly consistent (

Language: Английский

Citations

130
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies DOI Creative Commons
Fiona A. Hagenbeek, René Pool, Jenny van Dongen

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 7, 2020

Abstract Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences metabolite levels is due to genetic variance, but heritability estimates differ across classes. We perform a review all genome-wide association and (exome-) sequencing studies published between November 2008 October 2018, identify >800 class-specific loci associated with levels. In twin-family cohort ( N = 5117), these are leveraged simultaneously estimate (h 2 ), proportion captured by known Metabolite-hits ) for 309 lipids 52 organic acids. Our study reveals significant h among different classes Furthermore, phosphatidylcholines high degree unsaturation have higher than low degrees unsaturation. This highlights importance common variants levels, elucidates architecture

Language: Английский

Citations

91
Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations DOI Creative Commons
Daniel J. Panyard,

Kyeong Mo Kim,

Burcu F. Darst

et al.

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: Jan. 12, 2021

Abstract The study of metabolomics and disease has enabled the discovery new risk factors, diagnostic markers, drug targets. For neurological psychiatric phenotypes, cerebrospinal fluid (CSF) is particular importance. However, CSF metabolome difficult to on a large scale due relative complexity procedure needed collect fluid. Here, we present metabolome-wide association (MWAS), which uses genetic metabolomic data impute metabolites into samples with genome-wide summary statistics. We conduct metabolome-wide, analysis 338 metabolites, identifying 16 genotype-metabolite associations (metabolite quantitative trait loci, or mQTLs). then build prediction models for all available test 27 19 significant metabolite-phenotype associations. Our results demonstrate feasibility MWAS omic in scarce sample types.

Language: Английский

Citations

90
Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease DOI Creative Commons
Gemma Cadby, Corey Giles, Phillip E. Melton

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 6, 2022

Abstract We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism identify variants associated with species putatively in mechanistic pathway for coronary artery disease (CAD). quantified 596 serum from 4,492 individuals Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), validation two cohorts. A meta-analysis revealed an additional 70 species. 134 endophenotypes CAD 186 loci. Associations between atherosclerosis were assessed ∼456,000 UK Biobank. Of 53 that showed evidence association ( P < 1 × 10 −3 ), 43 loci at least one endophenotype. These findings illustrate value integrative biology investigate aetiology CAD, implications other complex diseases.

Language: Английский

Citations

67
Integrating lipidomics and genomics: emerging tools to understand cardiovascular diseases DOI Creative Commons
Rubina Tabassum, Samuli Ripatti

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(6), P. 2565 - 2584

Published: Jan. 15, 2021

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide to 31% all global deaths. Early prediction prevention could greatly reduce enormous socio-economic burden posed by CVDs. Plasma lipids have been at center stage strategies for CVDs that mostly relied on traditional (total cholesterol, total triglycerides, HDL-C LDL-C). The tremendous advancement in field lipidomics last two decades has facilitated research efforts unravel metabolic dysregulation their genetic determinants, enabling understanding pathophysiological mechanisms identification predictive biomarkers, beyond lipids. This review presents an overview application epidemiological studies contributions current field. We findings these discuss examples demonstrates potential revealing new biology not captured lipoprotein measurements. promising from raised opportunities fields personalized medicine further discusses prospects integrating emerging genomics tools with high-dimensional lipidome move forward statistical associations towards biological understanding, therapeutic target development risk prediction. believe holds a great but advancements computational needed handle correlated lipidome.

Language: Английский

Citations

57
The full spectrum of SLC22 OCT1 mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics DOI
Sook Wah Yee, Christian B. Macdonald, Darko Mitrovic

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(10), P. 1932 - 1947.e10

Published: May 1, 2024

Language: Английский

Citations

15