Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

• 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.

Ämnesord

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)

Nyckelord

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

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)