Evidence map›Paper›PMID 41466414›Full record

SynthesisOrphanet journal of rare diseases2025

Genome-wide association for sarcoidosis identifies novel risk loci and genetic heritability in African and European ancestries: a meta-analysis from the Finngen, Million Veteran Program, UK Biobank, and Biobank Japan datasets.

Andrea Ricci, Federica Andolfi, Daniele Sabbatini, Filippo Gozzi, Giada Di Betto, Paolo Ventura, Elena Buzzetti, Antonello Pietrangelo, Enrico Clini, Roberto Tonelli and 8 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Andrea RicciCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy. andrea.ricci@unimore.it.ORCID 0000-0002-4812-3750
Federica AndolfiCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy.
Daniele SabbatiniDepartment of Neurosciences Dns, University of Padova, Padova, Italy.
Filippo GozziCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy. filippo.gozzi@unimore.it.
Giada Di BettoCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy.
Paolo VenturaCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy.
Elena BuzzettiCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy.
Antonello PietrangeloCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy.
Enrico CliniCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy.
Roberto TonelliCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy.
Dario AndrisaniCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy.
Brent Julius de Guzman MarinduqueSchool of Medicine and Surgery, University of Modena and Reggio Emilia, Modena, Italy.
Elisa BergaminiInternal Medicine Unit, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
Chiara VecchiInternal Medicine Unit, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
Elena PegoraroDepartment of Neurosciences Dns, University of Padova, Padova, Italy.
Dario GregoriUnit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padova, Padova, Italy.
Elena CorradiniCentre for Genomic Medicine and Rare Diseases, Internal Medicine Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71,41121, Modena, Italy.
Stefania CerriCentre for Rare Lung Diseases, Pneumology Unit, Department of Medical and Surgical Sciences, University Hospital of Modena - Policlinico, ERN Lung, University of Modena and Reggio Emilia,Via del Pozzo 71, 41121, Modena, Italy.

Funding

Italian funds for Departments of Excellence
6 · The paper itself

Abstract

introductionSarcoidosis is an inflammatory disease driven by immune-mediated mechanisms, characterized by the formation of epithelioid cell granulomas and a wide range of clinical manifestations. Its phenotype is the result of a complex interplay of genetic and environmental factors, the precise roles and interactions of which remain poorly defined.

aimTo identify candidate genes and risk loci associated with sarcoidosis from large population datasets. To estimate the genetic heritability of the phenotype in selected ancestries. POPULATION AND

methodsPublic summary statistics from the FinnGen release 12 (European ancestry), pan UK BioBank Project (UKBB - European and African ancestry), Million Veteran Program (MVP - European and African ancestry), and Japan BioBank (East Asian ancestry) were included for European, African and multi-ancestry meta-analysis through sample size-based analysis. Novel risk loci and single nucleotide polymorphisms (SNPs) significantly associated with the disease were critically reviewed on the basis of the available literature. For each risk locus, SNPs highly correlated with the lead SNP were selected based on Combined Annotation Dependent Depletion (CADD) scores. Genetic heritability (h2) scores were obtained through ancestry-specific linkage-disequilibrium score calculation.

resultOverall 9659 cases (7559 European, 1880 African, 220 East Asian) and 1,665,804 controls (1,361,726 European, 126,411 African, 177,667 East Asian) were analysed. Nineteen and two risk loci were identified in European and African ancestry, respectively; h2 scores were 0.25 (European) and 0.19 (African). Candidate non-MHC genes for further explorations through functional studies included IL23R, PUS10, ACOXL, PLCL1, FAM117B, BMPR2, PPARG, ESYT2, ANXA11, CCDC88B, ATXN2, CCL24, RP11−540O11.1, HOMER2, CD19, UBASH3A, RNF215, and others. Interferon gamma signaling, meiotic recombination/condensation of prophase chromosomes, and DNA methylation were the most enriched gene sets in European and multi-ancestry meta-analysis. Multi-ancestry meta-analysis was confronted with FinnGen+UKBB+MVP meta-analysis (released by FinnGen freeze 12) yielding consistent results (18 risk loci identified)

conclusionNineteen and two risk loci were significantly associated with sarcoidosis for European and African ancestries, respectively. Moderate genetic heritability was observed for both ancestries. A set of significantly associated non-MHC genes and SNPs was obtained to investigate functional validation. Although further studies are warranted, epigenetic alterations may contribute to the risk of developing sarcoidosis

Indexed as

Genome-Wide Association StudySarcoidosisAfrican PeopleBiological Specimen BanksBlack PeopleEuropean PeopleGenetic Predisposition to DiseaseHumansJapanPolymorphism, Single NucleotideUnited KingdomWhiteWhite PeopleBiobank JapanFinnGenGWASMeta-analysisMillion veteran programRare diseasesSarcoidosisUK Biobank

Identifiers

PMID41466414
PMCPMC12751437

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.