Evidence map›Paper›PMID 36055244›Full record

ArticleAmerican journal of human genetics2022

Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk.

Xianyong Yin, Debraj Bose, Annie Kwon, Sarah C Hanks, Anne U Jackson, Heather M Stringham, Ryan Welch, Anniina Oravilahti, Lilian Fernandes Silva, FinnGen and 20 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 57 citations in OpenAlex.

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  7. A trans-omics gene-smoking interaction study of lung cancer based on consortium data.American journal of respiratory and critical care medicine · 2026
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  10. Multi-omics integration andFrontiers in immunology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 11 institutions in 3 countries.

Xianyong YinDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Debraj BoseDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Annie KwonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Sarah C HanksDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Ryan WelchDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Anniina OravilahtiInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
Lilian Fernandes SilvaInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
FinnGen
Adam E LockeMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO 63108, USA.
Christian FuchsbergerDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Institute for Biomedicine, Eurac Research, Bolzano 39100, Italy.
Susan K ServiceCenter for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90024, USA.
Michael R ErdosMolecular Genetics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lori L BonnycastleMolecular Genetics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Johanna KuusistoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland; Center for Medicine and Clinical Research, Kuopio University Hospital, Kuopio 70210, Finland.
Nathan O StitzielMcDonnell Genome Institute, Washington University School of Medicine, St Louis, MO 63108, USA; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Ira M HallCenter for Genomic Health, Department of Genetics, Yale University, New Haven, CT 06510, USA.
Jean MorrisonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Samuli RipattiInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki 00290, Finland; Department of Public Health, University of Helsinki, Helsinki 00014, Finland; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aarno PalotieInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki 00290, Finland; Department of Public Health, University of Helsinki, Helsinki 00014, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.
Nelson B FreimerCenter for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90024, USA.
Francis S CollinsMolecular Genetics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Karen L MohlkeDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Laura J ScottDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Eric B FaumanInternal Medicine Research Unit, Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA.
Charles BurantDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland. Electronic address: markku.laakso@uef.fi.
Xiaoquan WenDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: xwen@umich.edu.
University of Michigan · USUniversity of Eastern Finland · FINational Institutes of Health · USJames S. McDonnell Foundation · USUniversity of California, Los Angeles · USBroad Institute · USEurac Research · ITPfizer (United States) · USUniversity of Helsinki · FIUniversity of North Carolina at Chapel Hill · USYale University · US

Funding

Supplement Proposal: Accelerated Genome Aggregation and Joint Variant Calling EffortUM1HG008853 · NHGRI · WASHINGTON UNIVERSITY · PI HALL, IRA M, MILBRANDT, JEFFREY D · 2016 to 2020
$76.2M
Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
Triglycerides, Diabetes and Cardiovascular DiseaseP01HL151328 · NHLBI · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 2020 to 2026
$19.6M
University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4M
Identifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6M
Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3M
Genetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7M
GENETIC ANALYSIS OF TYPE II DIABETES IN FINNISH POPULATIONZ01HG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI COLLINS, FRANCIS S. · 1995 to 2008
$6.2M
Whole Genome Sequencing for Nephrotic Syndrome DiscoveryR01DK119380 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Dongwon Lee, MATTHEW Gordon SAMPSON · 2019 to 2026
$3.7M
ANGPTL3 DEFICIENCY AND ATHEROSCLEROSIS IN HUMANSR01HL131961 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2016 to 2020
$3.2M
Intramural NIH HHS Z01 HG000024Intramural NIH HHS ZIA HG000024NHGRI NIH HHS T32 HG000040NHGRI NIH HHS UM1 HG008853NHLBI NIH HHS P01 HL151328NHLBI NIH HHS R01 HL131961NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R01 DK119380NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U01 DK105561NIEHS NIH HHS R01 ES033634NIGMS NIH HHS R35 GM138121
6 · The paper itself

Abstract

Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite levels were more likely to influence gene expression and disease risk compared to the ones that do not. Integrating transcriptomics with metabolomics results prioritized 397 genes for 521 metabolites, including 496 previously identified gene-metabolite pairs with strong functional connections and suggested 33.3% of such gene-metabolite pairs shared the same causal variants with genetic associations of gene expression. Integrating transcriptomics and metabolomics individually with FinnGen GWAS results identified 1,597 genes for 790 disease traits. Integrating transcriptomics and metabolomics jointly with FinnGen GWAS results helped pinpoint metabolic pathways from genes to diseases. We identified putative causal effects of UGT1A1/UGT1A4 expression on gallbladder disorders through regulating plasma (E,E)-bilirubin levels, of SLC22A5 expression on nasal polyps and plasma carnitine levels through distinct pathways, and of LIPC expression on age-related macular degeneration through glycerophospholipid metabolic pathways. Our study highlights the power of integrating multiple sets of molecular traits and GWAS results to deepen understanding of disease pathophysiology.

Indexed as

Genome-Wide Association StudyTranscriptomeBilirubinCarnitineGlycerophospholipidsHumansMaleMetabolomicsQuantitative Trait LociSolute Carrier Family 22 Member 5BilirubinCarnitineGlycerophospholipidsSLC22A5 protein, humanSolute Carrier Family 22 Member 5colocalizataiongenome-wide association studymetabolomicstranscriptome-wide association studytranscriptomics

Identifiers

PMID36055244
PMCPMC9606383
OpenAlexW4294011225

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.