학술논문
Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.
Document Type
Academic Journal
Author
Rouskas K; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Institute of Applied Biosciences, Centre for Research & Technology Hellas, Thessaloniki, Greece.; Katsareli EA; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.; Amerikanou C; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.; Dimopoulos AC; Institute for Fundamental Biomedical Science, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Hellenic Naval Academy, Hatzikyriakou Avenue, Pireaus, Greece.; Glentis S; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Pediatric Hematology/Oncology Unit (POHemU), First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.; Kalantzi A; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Skoulakis A; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Panousis N; Wellcome Sanger Institute, Hinxton, UK.; Ongen H; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.; Swiss Institute of Bioinformatics, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.; Bielser D; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.; Planchon A; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.; Romano L; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.; Harokopos V; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Reczko M; Institute for Fundamental Biomedical Science, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Moulos P; Institute for Fundamental Biomedical Science, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.; Center of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Griniatsos I; First Department of Surgery, National and Kapodistrian University of Athens, Medical School, Laiko Hospital, Athens, Greece.; Diamantis T; First Department of Surgery, National and Kapodistrian University of Athens, Medical School, Laiko Hospital, Athens, Greece.; Dermitzakis ET; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.; Ragoussis J; Department of Human Genetics, McGill University Genome Centre, McGill University, Montréal, QC, Canada.; Department of Bioengineering, McGill University, Montréal, QC, Canada.; Dedoussis G; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.; Dimas AS; Institute for Bioinnovation, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece. dimas@fleming.gr.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource.
Results: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue.
Conclusions: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Results: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue.
Conclusions: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.
(© 2023. BioMed Central Ltd., part of Springer Nature.)