{"entity": "researcher", "timestamp": "2026-09-23T15:07:36.316Z", "family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "affiliations": ["Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3"}}, "publications": [{"entity": "publication", "iuid": "25b69f7c5468478a9d1638a6ec8decd3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/25b69f7c5468478a9d1638a6ec8decd3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/25b69f7c5468478a9d1638a6ec8decd3"}}, "title": "Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.", "authors": [{"family": "Christmas", "given": "Matthew J", "initials": "MJ", "orcid": "0000-0002-6355-7581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/997ea196d4ae4c9790a715246dbfac82.json"}}, {"family": "Dong", "given": "Michael X", "initials": "MX"}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS", "orcid": "0000-0002-0850-230X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f363e8d74594ffeb0d68aa6d774b242.json"}}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/612a779b69494f1ca9b6c5f1d84fd711.json"}}], "type": "journal article", "published": "2025-02-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "2007", "issn-l": "2041-1723"}, "abstract": "Mammalian genomes are biased towards GC bases at third codon positions, likely due to a GC-biased ancestral genome and the selectively neutral recombination-related process of GC-biased gene conversion. The unwanted transcript hypothesis posits that this high GC content at synonymous sites may be beneficial for protecting against spurious transcripts, particularly in species with low effective population sizes. Utilising a 240 placental mammal genome alignment and single-base resolution conservation scores, we interpret sequence conservation at mammalian four-fold degenerate sites in this context and find evidence in support of the unwanted transcript hypothesis, including a strong GC bias, high conservation at sites relating to exon splicing, less human genetic variation at conserved four-fold degenerate sites, and conservation of sites important for epigenetic regulation of developmental genes. Additionally, we show that high conservation of four-fold degenerate sites in essential developmental genes, including homeobox genes, likely relates to the low mutation rates experienced by these genes.", "doi": "10.1038/s41467-025-57179-w", "pmid": "40011430", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11865589"}, {"db": "pii", "key": "10.1038/s41467-025-57179-w"}], "notes": [], "created": "2026-09-23T11:34:57.061Z", "modified": "2026-09-23T11:34:57.159Z"}, {"entity": "publication", "iuid": "f8942a7836cc47c9ac266895832ee8f9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f8942a7836cc47c9ac266895832ee8f9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f8942a7836cc47c9ac266895832ee8f9"}}, "title": "Unraveling the Genetics of Shared Clinical and Serological Manifestations in Patients With Systemic Inflammatory Autoimmune Diseases.", "authors": [{"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3183e335a393486f8b6534db17b066d0.json"}}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}}, {"family": "Notarnicola", "given": "Antonella", "initials": "A", "orcid": "0000-0003-0272-2931", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/708cd9cafb384ed29732f2c5fb1a17bd.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK"}, {"family": "Pettersson", "given": "Mats", "initials": "M"}, {"family": "Leonard", "given": "Dag", "initials": "D"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9fcc24622ec440bac6996072cceea0e.json"}}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S", "orcid": "0000-0001-8259-3863", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c8c4d669b3942309a148980c1437b5d.json"}}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c44ebd4f33e46a1862877bce94be05b.json"}}, {"family": "Enocsson", "given": "Helena", "initials": "H", "orcid": "0000-0002-2125-2931", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/174462ef4f7c4f6381aa2fd4cc29569d.json"}}, {"family": "Kvarnstr\u00f6m", "given": "Marika", "initials": "M"}, {"family": "Forsblad-d'Elia", "given": "Helena", "initials": "H"}, {"family": "Bucher", "given": "Sara Magnusson", "initials": "SM"}, {"family": "Norheim", "given": "Katrine B", "initials": "KB"}, {"family": "Baecklund", "given": "Eva", "initials": "E"}, {"family": "Jonsson", "given": "Roland", "initials": "R"}, {"family": "Hammenfors", "given": "Daniel", "initials": "D"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Mandl", "given": "Thomas", "initials": "T"}, {"family": "Omdal", "given": "Roald", "initials": "R"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Andersson", "given": "Helena", "initials": "H"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Diederichsen", "given": "Louise Pyndt", "initials": "LP"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "Wahren-Herlenius", "given": "Marie", "initials": "M", "orcid": "0000-0002-0915-7245", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0db5190dbe894a5e9cd961e66ba5c75d.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f618934952594d76a747bcbe2c27bbf2.json"}}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE", "orcid": "0000-0002-6068-9212", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2891140c49d446dbd82c96857bcde73.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K"}, {"family": "with the DISSECT consortium and the ImmunoArray consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Arthritis & rheumatology (Hoboken, N.J.)", "issn": "2326-5205", "volume": "77", "issue": "2", "pages": "212-225", "issn-l": "2326-5191"}, "abstract": "Systemic inflammatory autoimmune diseases (SIADs) such as systemic lupus erythematosus (SLE), primary Sj\u00f6gren disease (pSS), and idiopathic inflammatory myopathies (myositis) are complex conditions characterized by shared circulating autoantibodies and clinical manifestations, including skin rashes, among others. This study was aimed at elucidating the genetics underlying these common features.\n\nWe performed targeted DNA sequencing of coding and regulatory regions from approximately 1,900 immune-related genes in a large cohort of 2,292 well-characterized Scandinavian patients with SIADs with SLE, pSS, and myositis as well as 1,252 controls. A gene-based functionally weighted genetic score for aggregate testing of all genetic variants, including rare variants, was complemented by in silico functional analyses and in vitro reporter experiments.\n\nCase-control association analysis detected known and potentially novel genetic loci in agreement with previous genetic and transcriptomics findings linked to the SIAD autoimmune background. Intriguingly, case-case comparisons between patient subgroups with and without specific autoantibodies revealed that the subgroups defined by antinuclear antibodies and anti-double-stranded DNA antibodies have unique genetic profiles reflecting their heterogeneity. When focusing on clinical features, we overall showed that dual-specificity phosphatase 1 (DUSP1) protective genetic variants lead to increased gene expression and potentially to anti-inflammatory effects on the SIAD-associated skin phenotype. This is consistent with recent genetic findings on eczema and with the previously reported down-regulation of the MAPK signaling-related gene DUSP1 in other skin disorders.\n\nTogether, this suggests common molecular mechanisms potentially underlying overlapping clinical manifestations shared among different disorders and informs clinical heterogeneity, which could be translated to improve disease diagnostic and treatment, also in more generalized disease frameworks.", "doi": "10.1002/art.42988", "pmid": "39284741", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11782108"}], "notes": [], "created": "2026-09-23T12:19:32.987Z", "modified": "2026-09-23T12:19:33.106Z"}, {"entity": "publication", "iuid": "b9fd8cd4df2f4cfd90ea1c40bf40619e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b9fd8cd4df2f4cfd90ea1c40bf40619e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b9fd8cd4df2f4cfd90ea1c40bf40619e"}}, "title": "Evolutionary constraint and innovation across hundreds of placental mammals.", "authors": [{"family": "Christmas", "given": "Matthew J", "initials": "MJ", "orcid": "0000-0002-6355-7581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/997ea196d4ae4c9790a715246dbfac82.json"}}, {"family": "Kaplow", "given": "Irene M", "initials": "IM", "orcid": "0000-0002-8924-8269", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fc8b6ee363a4ccaaea909392715888a.json"}}, {"family": "Genereux", "given": "Diane P", "initials": "DP", "orcid": "0000-0001-5770-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/352ee25047c544aaa486a69e7e3333fc.json"}}, {"family": "Dong", "given": "Michael X", "initials": "MX", "orcid": "0000-0003-4084-3099", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/acaddec22cd64c8aaec92764cd4adf08.json"}}, {"family": "Hughes", "given": "Graham M", "initials": "GM", "orcid": "0000-0003-3088-345X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9785e94b95a3466dbb70ad8eb9b34ccd.json"}}, {"family": "Li", "given": "Xue", "initials": "X", "orcid": "0000-0002-9126-2692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5766930b7e3946e5a3f2e268605ab97b.json"}}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF", "orcid": "0000-0002-6619-873X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0c59458e7834499cbe990b1f9b83236c.json"}}, {"family": "Hindle", "given": "Allyson G", "initials": "AG", "orcid": "0000-0002-1983-9573", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49459b37810943aca91c847060596160.json"}}, {"family": "Andrews", "given": "Gregory", "initials": "G", "orcid": "0000-0002-9880-3965", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b10e5f60ff3241758e65b9dca69fad7b.json"}}, {"family": "Armstrong", "given": "Joel C", "initials": "JC"}, {"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3183e335a393486f8b6534db17b066d0.json"}}, {"family": "Breit", "given": "Ana M", "initials": "AM", "orcid": "0000-0002-4990-3353", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/db59adc2e4054528823c09df71a8c299.json"}}, {"family": "Diekhans", "given": "Mark", "initials": "M", "orcid": "0000-0002-0430-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7999277bf08b4dbdbcc7d5e78cafcb00.json"}}, {"family": "Fanter", "given": "Cornelia", "initials": "C", "orcid": "0000-0002-4591-1866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e011e81556cb445fb045b25f9c0cf7dc.json"}}, {"family": "Foley", "given": "Nicole M", "initials": "NM", "orcid": "0000-0002-8169-9436", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/109dac01ce9c443cbbe73e3d0d4f0f2f.json"}}, {"family": "Goodman", "given": "Daniel B", "initials": "DB", "orcid": "0000-0003-3759-6883", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b6e135269904a95be06f115902bd26d.json"}}, {"family": "Goodman", "given": "Linda", "initials": "L", "orcid": "0000-0002-7830-5897", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49cf8685b504423abe0cdcd0c9e07dd7.json"}}, {"family": "Keough", "given": "Kathleen C", "initials": "KC", "orcid": "0000-0002-7481-0511", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/27ba6707b77e4d0eb914e71063dab333.json"}}, {"family": "Kirilenko", "given": "Bogdan", "initials": "B", "orcid": "0000-0002-9394-4275", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/453bbdef3a5c49bcb8ecddb2f3e8279f.json"}}, {"family": "Kowalczyk", "given": "Amanda", "initials": "A", "orcid": "0000-0002-9061-1336", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71441a08bca44979aac0e9aa8fa44cdf.json"}}, {"family": "Lawless", "given": "Colleen", "initials": "C", "orcid": "0000-0002-4454-7994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/03534b53cce14bb1a92bbace87d46709.json"}}, {"family": "Lind", "given": "Abigail L", "initials": "AL", "orcid": "0000-0002-9579-4178", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d713070f6803498b87547e09217b2706.json"}}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS", "orcid": "0000-0002-0850-230X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f363e8d74594ffeb0d68aa6d774b242.json"}}, {"family": "Moreira", "given": "Lucas R", "initials": "LR", "orcid": "0000-0002-9084-3954", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f527c1e52514bc0b08885355418fa12.json"}}, {"family": "Redlich", "given": "Ruby W", "initials": "RW"}, {"family": "Ryan", "given": "Louise", "initials": "L", "orcid": "0000-0002-6876-677X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0270b6be6758495ca9c12b9c73b804aa.json"}}, {"family": "Swofford", "given": "Ross", "initials": "R", "orcid": "0000-0003-3676-8479", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85b0174c633b417b933092763175bb1c.json"}}, {"family": "Valenzuela", "given": "Alejandro", "initials": "A", "orcid": "0000-0002-2252-3887", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0071ff283e894309b48866a1f982bc9a.json"}}, {"family": "Wagner", "given": "Franziska", "initials": "F"}, {"family": "Wallerman", "given": "Ola", "initials": "O", "orcid": "0000-0003-1037-7904", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/567836f4582a4f79b9fbb362c656b8c9.json"}}, {"family": "Brown", "given": "Ashley R", "initials": "AR", "orcid": "0000-0002-3091-3930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74b99a2a10ea4d4c995e6fd3fff65fe6.json"}}, {"family": "Damas", "given": "Joana", "initials": "J", "orcid": "0000-0003-4857-2510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f60eb6afeabc435ea1e6378786162fa8.json"}}, {"family": "Fan", "given": "Kaili", "initials": "K", "orcid": "0000-0002-8723-7902", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc1e106eea64c4db31946a4067fd605.json"}}, {"family": "Gatesy", "given": "John", "initials": "J", "orcid": "0000-0003-3061-7741", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bcb8754ebea546b8936fc450255afc21.json"}}, {"family": "Grimshaw", "given": "Jenna", "initials": "J", "orcid": "0000-0001-7673-5167", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/47c81a9b846f488d9b140dcfcb28edaf.json"}}, {"family": "Johnson", "given": "Jeremy", "initials": "J", "orcid": "0000-0001-8548-5972", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ec69a3f2cdf4e3bbe0fb10a53c45fea.json"}}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}}, {"family": "Lawler", "given": "Alyssa J", "initials": "AJ", "orcid": "0000-0002-2151-5164", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb3c0a5c01064277918e610c2e6f97d7.json"}}, {"family": "Marinescu", "given": "Voichita D", "initials": "VD", "orcid": "0000-0002-4803-4707", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/01f46abb4cbc4f269440556154454ebb.json"}}, {"family": "Morrill", "given": "Kathleen M", "initials": "KM", "orcid": "0000-0002-9139-453X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5176e46101684ebf9f1b906efc570261.json"}}, {"family": "Osmanski", "given": "Austin", "initials": "A", "orcid": "0000-0002-1485-6446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d9dda01496474b11a018f3c629f18d1b.json"}}, {"family": "Paulat", "given": "Nicole S", "initials": "NS", "orcid": "0000-0002-6881-2588", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ca5ca8c8acd4c65b5836fecb4b443a0.json"}}, {"family": "Phan", "given": "BaDoi N", "initials": "BN", "orcid": "0000-0001-6331-5980", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ba10919dc8445f9bf68539551f47c17.json"}}, {"family": "Reilly", "given": "Steven K", "initials": "SK", "orcid": "0000-0003-3140-1483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dea3d4ff8a9643d196e3f3fd1ded79d4.json"}}, {"family": "Sch\u00e4ffer", "given": "Daniel E", "initials": "DE", "orcid": "0000-0003-3608-152X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b7f399939ae14daa8c0bd9bf5b92a896.json"}}, {"family": "Steiner", "given": "Cynthia", "initials": "C", "orcid": "0000-0002-2131-8072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9386c16bd7e14ddca60e03e06f6808fe.json"}}, {"family": "Supple", "given": "Megan A", "initials": "MA", "orcid": "0000-0002-0204-7852", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/073a9fab924c4e96973f1e23accaa7ae.json"}}, {"family": "Wilder", "given": "Aryn P", "initials": "AP", "orcid": "0000-0003-4970-6891", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b080282d4674df1bde072812bf448be.json"}}, {"family": "Wirthlin", "given": "Morgan E", "initials": "ME", "orcid": "0000-0001-7967-7070", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b1757207aa24108859d7c116bda19b7.json"}}, {"family": "Xue", "given": "James R", "initials": "JR", "orcid": "0000-0002-3332-5747", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd4a26d78f1547c7865cab2847ab0d6b.json"}}, {"family": "Zoonomia Consortium\u00a7", "given": "", "initials": ""}, {"family": "Birren", "given": "Bruce W", "initials": "BW"}, {"family": "Gazal", "given": "Steven", "initials": "S", "orcid": "0000-0003-4510-5730", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/992edd7528434c7b900b8d531f18b15c.json"}}, {"family": "Hubley", "given": "Robert M", "initials": "RM", "orcid": "0000-0001-9261-3821", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/86b6fe3c9be54bc58dd8c750dda51aa3.json"}}, {"family": "Koepfli", "given": "Klaus-Peter", "initials": "KP"}, {"family": "Marques-Bonet", "given": "Tomas", "initials": "T", "orcid": "0000-0002-5597-3075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1091cb5bfe394d459969d24bb1c22c66.json"}}, {"family": "Meyer", "given": "Wynn K", "initials": "WK", "orcid": "0000-0001-7978-3877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4b1fba9de46a4c8c8cbbbec685a9b94c.json"}}, {"family": "Nweeia", "given": "Martin", "initials": "M", "orcid": "0000-0001-7079-4123", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b4846b6d146a4a7288db1543583a0158.json"}}, {"family": "Sabeti", "given": "Pardis C", "initials": "PC", "orcid": "0000-0002-9843-1890", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6848f42df6b146df8fd953c169193eb4.json"}}, {"family": "Shapiro", "given": "Beth", "initials": "B", "orcid": "0000-0002-2733-7776", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8f15a636469944ddb56489a74a75591b.json"}}, {"family": "Smit", "given": "Arian F A", "initials": "AFA", "orcid": "0000-0003-2088-3165", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ddf0080c6ee44cbe830114f0ab126884.json"}}, {"family": "Springer", "given": "Mark S", "initials": "MS", "orcid": "0000-0001-7335-6946", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93985cf0515345b8b302228258be970e.json"}}, {"family": "Teeling", "given": "Emma C", "initials": "EC", "orcid": "0000-0002-3309-1346", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28069443db794cb596e58aea060d9dea.json"}}, {"family": "Weng", "given": "Zhiping", "initials": "Z", "orcid": "0000-0002-3032-7966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22242b8810024fa6b7c098ced475db12.json"}}, {"family": "Hiller", "given": "Michael", "initials": "M", "orcid": "0000-0003-3024-1449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1005d0d1f4264b46b1cfe214c7aca246.json"}}, {"family": "Levesque", "given": "Danielle L", "initials": "DL", "orcid": "0000-0003-0132-8094", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/291c0db9f1014708bfe1c52a946e1df7.json"}}, {"family": "Lewin", "given": "Harris A", "initials": "HA", "orcid": "0000-0002-1043-7287", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5059da24204049c696aec45b62526759.json"}}, {"family": "Murphy", "given": "William J", "initials": "WJ", "orcid": "0000-0003-3699-0723", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a71bcbcd8a6437ea7c32ce512ebd38c.json"}}, {"family": "Navarro", "given": "Arcadi", "initials": "A", "orcid": "0000-0003-2162-8246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8360a54a1b447d0b67d85b3f1e40b5a.json"}}, {"family": "Paten", "given": "Benedict", "initials": "B", "orcid": "0000-0001-8863-3539", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c916e24b35f2459480cf87e27bb21ee1.json"}}, {"family": "Pollard", "given": "Katherine S", "initials": "KS", "orcid": "0000-0002-9870-6196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d080bc9bff548958f0c161612cdc4cf.json"}}, {"family": "Ray", "given": "David A", "initials": "DA", "orcid": "0000-0002-3340-3987", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6392a5497414b98999823cbafd67d4b.json"}}, {"family": "Ruf", "given": "Irina", "initials": "I", "orcid": "0000-0002-9728-1210", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cbc58d9ceb8d490baab61cb6002cecbe.json"}}, {"family": "Ryder", "given": "Oliver A", "initials": "OA", "orcid": "0000-0003-2427-763X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d18635ed6fa42d4bbcfddadae70e308.json"}}, {"family": "Pfenning", "given": "Andreas R", "initials": "AR", "orcid": "0000-0002-3447-9801", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f7c2be6e32147d19f03c7ff88fb3f80.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/612a779b69494f1ca9b6c5f1d84fd711.json"}}, {"family": "Karlsson", "given": "Elinor K", "initials": "EK", "orcid": "0000-0002-4343-3776", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/81b5c82fcb904394b6a6b1d811863fa0.json"}}], "type": "journal article", "published": "2023-04-28", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "380", "issue": "6643", "pages": "eabn3943", "issn-l": "0036-8075"}, "abstract": "Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.", "doi": "10.1126/science.abn3943", "pmid": "37104599", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1896905"}, {"db": "pmc", "key": "PMC10250106"}], "notes": [], "created": "2026-09-23T06:39:33.319Z", "modified": "2026-09-23T06:39:34.893Z"}, {"entity": "publication", "iuid": "5f5bd98bdc044b8faf1be206e871b7b2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5f5bd98bdc044b8faf1be206e871b7b2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5f5bd98bdc044b8faf1be206e871b7b2"}}, "title": "Mer-tyrosine kinase: a novel susceptibility gene for SLE related end-stage renal disease.", "authors": [{"family": "Yavuz", "given": "Sule", "initials": "S"}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8d564c4e36f451f9b78f563c9e8fa07.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5bbdb0cf40c48198ea04ede2fb33377.json"}}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/444ae7021f634df8b55e61c85c81b28b.json"}}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}}, {"family": "Lanata", "given": "Cristina M", "initials": "CM"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9fcc24622ec440bac6996072cceea0e.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c44ebd4f33e46a1862877bce94be05b.json"}}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "ImmunoArray Development Consortium", "given": "", "initials": ""}, {"family": "DISSECT Consortium", "given": "", "initials": ""}, {"family": "Nititham", "given": "Joanne", "initials": "J"}, {"family": "Criswell", "given": "Lindsey A", "initials": "LA"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f7ec7a7befd44cc988091ba0858d3c0.json"}}], "type": "meta-analysis", "published": "2022-11-00", "journal": {"title": "Lupus Sci Med", "issn": "2053-8790", "volume": "9", "issue": "1", "issn-l": null}, "abstract": "Lupus nephritis (LN) is a common and severe manifestation of SLE. The genetic risk for nephritis and progression to end-stage renal disease (ESRD) in patients with LN remains unclear. Herein, we aimed to identify novel genetic associations with LN, focusing on subphenotypes and ESRD.\n\nWe analysed genomic data on 958 patients with SLE (discovery cohort: LN=338) with targeted sequencing data from 1832 immunological pathway genes. We used an independent multiethnic cohort comprising 1226 patients with SLE (LN=603) as a replication dataset. Detailed functional annotation and functional epigenomic enrichment analyses were applied to predict functional effects of the candidate variants.\n\nA genetic variant (rs56097910) within the MERTK gene was associated with ESRD in both cohorts, meta-analysis OR=5.4 (2.8 to 10.6); p=1.0\u00d710-6. We observed decreased methylation levels in peripheral blood cells from SLE patients with ESRD, compared with patients without renal SLE (p=2.7\u00d710-4), at one CpG site (cg16333401) in close vicinity to the transcription start site of MERTK and located in a DNAse hypersensitivity region in T and B cells. Rs56097910 is linked to altered MERTK expression in kidney tissue in public eQTL databases. Two loci were replicated for association with proliferative LN: PRDM1 (rs6924535, pmeta=1.6\u00d710-5, OR=0.58) and APOA1BP (NAXE) (rs942960, pmeta=1.2\u00d710-5, OR=2.64).\n\nWe identified a novel genetic risk locus, MERTK, associated with SLE-ESRD using the data from two large SLE cohorts. Through DNA methylation analysis and functional annotation, we showed that the risk could be mediated through regulation of gene expression. Our results suggest that variants in the MERTK gene are important for the risk of developing SLE-ESRD and suggest a role for PRDM1 and APOA1BP in proliferative LN.", "doi": "10.1136/lupus-2022-000752", "pmid": "36332927", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9639142"}, {"db": "pii", "key": "9/1/e000752"}], "notes": [], "created": "2026-09-23T12:11:39.258Z", "modified": "2026-09-23T12:11:39.343Z"}, {"entity": "publication", "iuid": "e1ece15c11e14b8d8cd0d18214fda961", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e1ece15c11e14b8d8cd0d18214fda961.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e1ece15c11e14b8d8cd0d18214fda961"}}, "title": "Contribution of Rare Genetic Variation to Disease Susceptibility in a Large Scandinavian Myositis Cohort.", "authors": [{"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3183e335a393486f8b6534db17b066d0.json"}}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cef7ddc40d8f47468f3f3dec3caa5de3.json"}}, {"family": "Notarnicola", "given": "Antonella", "initials": "A", "orcid": "0000-0003-0272-2931", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/708cd9cafb384ed29732f2c5fb1a17bd.json"}}, {"family": "Hultin Rosenberg", "given": "Lina", "initials": "L"}, {"family": "Karlsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8d564c4e36f451f9b78f563c9e8fa07.json"}}, {"family": "Rothwell", "given": "Simon", "initials": "S", "orcid": "0000-0003-2123-9902", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e28d139b79e4cf9a76140fd2ae830b3.json"}}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5bbdb0cf40c48198ea04ede2fb33377.json"}}, {"family": "Andersson", "given": "Helena", "initials": "H"}, {"family": "Cooper", "given": "Robert G", "initials": "RG"}, {"family": "Padyukov", "given": "Leonid", "initials": "L", "orcid": "0000-0003-2950-5670", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/336dfd4ed41542338e3aae1e29ce1da2.json"}}, {"family": "Tj\u00e4rnlund", "given": "Anna", "initials": "A"}, {"family": "Dastmalchi", "given": "Maryam", "initials": "M"}, {"family": "ImmunoArray Development Consortium", "given": "", "initials": ""}, {"family": "DISSECT Consortium", "given": "", "initials": ""}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS", "orcid": "0000-0002-0850-230X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f363e8d74594ffeb0d68aa6d774b242.json"}}, {"family": "Pyndt Diederichsen", "given": "Louise", "initials": "L"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Chinoy", "given": "Hector", "initials": "H", "orcid": "0000-0001-6492-1288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3d7de322dd44925adf4ffdc01365f8f.json"}}, {"family": "Lamb", "given": "Janine A", "initials": "JA", "orcid": "0000-0002-7248-0539", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/07cd7a5b44b54240aa81d5f257743da4.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f7ec7a7befd44cc988091ba0858d3c0.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/612a779b69494f1ca9b6c5f1d84fd711.json"}}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE", "orcid": "0000-0002-6068-9212", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2891140c49d446dbd82c96857bcde73.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Arthritis & rheumatology (Hoboken, N.J.)", "issn": "2326-5205", "volume": "74", "issue": "2", "pages": "342-352", "issn-l": "2326-5191"}, "abstract": "Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.\n\nTargeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case-control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant- and gene-level enrichment analyses, was implemented to explore genotype-phenotype relations.\n\nGene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle-specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.\n\nOur study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.", "doi": "10.1002/art.41929", "pmid": "34279065", "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T12:01:09.322Z", "modified": "2026-09-23T12:01:09.576Z"}]}