{"entity": "publication", "iuid": "3a024c613f6f4432bebc3a69a15da709", "timestamp": "2026-09-03T05:35:04.548Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3a024c613f6f4432bebc3a69a15da709.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3a024c613f6f4432bebc3a69a15da709"}}, "title": "A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.", "authors": [{"family": "Timmons", "given": "James A", "initials": "JA"}, {"family": "Atherton", "given": "Philip J", "initials": "PJ"}, {"family": "Larsson", "given": "Ola", "initials": "O"}, {"family": "Sood", "given": "Sanjana", "initials": "S"}, {"family": "Blokhin", "given": "Ilya O", "initials": "IO"}, {"family": "Brogan", "given": "Robert J", "initials": "RJ"}, {"family": "Volmar", "given": "Claude-Henry", "initials": "CH"}, {"family": "Josse", "given": "Andrea R", "initials": "AR"}, {"family": "Slentz", "given": "Cris", "initials": "C"}, {"family": "Wahlestedt", "given": "Claes", "initials": "C"}, {"family": "Phillips", "given": "Stuart M", "initials": "SM"}, {"family": "Phillips", "given": "Bethan E", "initials": "BE"}, {"family": "Gallagher", "given": "Iain J", "initials": "IJ"}, {"family": "Kraus", "given": "William E", "initials": "WE"}], "type": "journal article", "published": "2018-09-06", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "46", "issue": "15", "pages": "7772-7792", "issn-l": "0305-1048"}, "abstract": "Genome-wide association studies (GWAS), relying on hundreds of thousands of individuals, have revealed >200 genomic loci linked to metabolic disease (MD). Loss of insulin sensitivity (IS) is a key component of MD and we hypothesized that discovery of a robust IS transcriptome would help reveal the underlying genomic structure of MD. Using 1,012 human skeletal muscle samples, detailed physiology and a tissue-optimized approach for the quantification of coding (>18,000) and non-coding (>15,000) RNA (ncRNA), we identified 332 fasting IS-related genes (CORE-IS). Over 200 had a proven role in the biochemistry of insulin and/or metabolism or were located at GWAS MD loci. Over 50% of the CORE-IS genes responded to clinical treatment; 16 quantitatively tracking changes in IS across four independent studies (P = 0.0000053: negatively: AGL, G0S2, KPNA2, PGM2, RND3 and TSPAN9 and positively: ALDH6A1, DHTKD1, ECHDC3, MCCC1, OARD1, PCYT2, PRRX1, SGCG, SLC43A1 and SMIM8). A network of ncRNA positively related to IS and interacted with RNA coding for viral response proteins (P < 1 \u00d7 10-48), while reduced amino acid catabolic gene expression occurred without a change in expression of oxidative-phosphorylation genes. We illustrate that combining in-depth physiological phenotyping with robust RNA profiling methods, identifies molecular networks which are highly consistent with the genetics and biochemistry of human metabolic disease.", "doi": "10.1093/nar/gky570", "pmid": "29986096", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6125682"}, {"db": "pii", "key": "5050628"}], "notes": [], "created": "2026-08-20T09:50:29.315Z", "modified": "2026-08-20T09:50:29.371Z"}