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Kasela, S.* ; Aguet, F.* ; Kim-Hellmuth, S. ; Brown, B.C.* ; Nachun, D.C.* ; Tracy, R.P.* ; Durda, P.* ; Liu, Y.* ; Taylor, K.D.* ; Johnson, W.C.* ; van Den Berg, D.* ; Gabriel, S.* ; Gupta, N.* ; Smith, J.D.* ; Blackwell, T.W.* ; Rotter, J.I.* ; Ardlie, K.G.* ; Manichaikul, A.* ; Rich, S.S.* ; Barr, R.G.* ; Lappalainen, T.*

Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects.

Am. J. Hum. Genet. 111, 133-149 (2024)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dna Methylation ; Cell-type Composition ; Gene Expression ; Gene-environment Interaction ; Interaction Qtl; Integrative Analysis; Expression; Methylation; Disease; Innate; System; Risk; Loci; Eqtl
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 111, Heft: 1, Seiten: 133-149 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
Förderungen NHLBI
NIH's National Institute of General Medical Sciences
NHGRI
National Institute of Mental Healthof the NIH
NIH's National Human Genome Research Institute (NHGRI)
Deutsche Forschungsgemeinschaft
Helmholtz Young Investigator grant
Marie-Sk1odowska Curie fellowship H2020 grant
National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH)