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Genetic analysis of...
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
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- Brown, A.A. (author)
- Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom
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- Giordano, G.N. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Ridderstråle, M. (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Franks, P.W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Atabaki-Pasdar, N. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Fitipaldi, H. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Groop, L. (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Klintenberg, M. (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Pomares-Millan, H. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Viñuela, A. (author)
- Biosciences Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, NE1 4EP, United Kingdom
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- Hong, Mun-Gwan (author)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
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- Uhlén, Mathias (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Schwenk, Jochen M. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Science for Life Laboratory, School of Biotechnology, KTH - Royal Institute of Technology, Solna, SE-171 21, Sweden
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(creator_code:org_t)
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- Springer Nature, 2023
- 2023
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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https://doi.org/10.1...
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Abstract
Subject headings
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- We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue. © 2023, Springer Nature Limited.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Genomics
- Humans
- Multifactorial Inheritance
- Phenotype
- Research Personnel
- RNA, Messenger
- messenger RNA
- plasma protein
- protein kinase Lck
- transcription factor
- blood
- gene expression
- genetic analysis
- phenotype
- protein
- RNA
- 5' untranslated region
- adult
- aged
- Article
- biochemical analysis
- cohort analysis
- DNA extraction
- donor
- exon
- fasting blood glucose level
- female
- functional enrichment analysis
- gene linkage disequilibrium
- genetic association
- genetic heterogeneity
- genetic regulation
- genetic variation
- genome-wide association study
- genotyping
- human
- impaired glucose tolerance
- major clinical study
- male
- mitochondrion
- non insulin dependent diabetes mellitus
- pancreas islet
- phenotypic variation
- pleiotropy
- proteomics
- quantitative trait locus
- RNA sequencing
- single nucleotide polymorphism
- transcription regulation
- Y chromosome
- genomics
- multifactorial inheritance
- personnel
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Brown, A.A.
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Giordano, G.N.
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Ridderstråle, M.
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Franks, P.W.
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Atabaki-Pasdar, ...
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Fitipaldi, H.
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show more...
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Groop, L.
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Klintenberg, M.
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Pomares-Millan, ...
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Viñuela, A.
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Hong, Mun-Gwan
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Uhlén, Mathias
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Schwenk, Jochen ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Royal Institute of Technology