Evidence map›Paper›PMID 37789421›Full record

ArticleHuman genomics2023

Whole-exome sequencing reveals candidate high-risk susceptibility genes for endometriosis.

Susanna Nousiainen, Outi Kuismin, Siiri Reinikka, Roosa Manninen, Sara Khamaiseh, Mari Kuivalainen, Anna Terho, Sari Koivurova, Maarit Niinimäki, Kari Salokas and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. The role ofFrontiers in immunology · 2026
    Article
  2. Monogenic Contributions to Familial Endometriosis: A Scoping Review.Gynecologic and obstetric investigation · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. 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

16 authors at 6 institutions in 1 country.

Susanna NousiainenApplied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland.
Outi KuisminDepartment of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
Siiri ReinikkaApplied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland.
Roosa ManninenResearch Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Sara KhamaisehApplied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland.
Mari KuivalainenDepartment of Obstetrics and Gynecology, Kainuu Central Hospital, Kajaani, Finland.
Anna TerhoResearch Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Sari KoivurovaResearch Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Maarit NiinimäkiResearch Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Kari SalokasInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Markku VarjosaloInstitute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Anne AhtikoskiDepartment of Pathology, Turku University Hospital, Turku, Finland.
Ralf BützowApplied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland.
Outi LindgrenResearch Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
Outi UimariMedical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
Pia VahteristoApplied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland. pia.vahteristo@helsinki.fi.
University of Helsinki · FIOulu University Hospital · FIUniversity of Oulu · FIHelsinki University Hospital · FIKajaani University of Applied Sciences · FITurku University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndometriosis is a common, chronic disease among fertile-aged women. Disease course may be highly invasive, requiring extensive surgery. The etiology of endometriosis remains elusive, though a high level of heritability is well established. Several low-penetrance predisposing loci have been identified, but high-risk susceptibility remains undetermined. Endometriosis is known to increase the risk of epithelial ovarian cancers, especially of endometrioid and clear cell types. Here, we have analyzed a Finnish family where four women have been diagnosed with surgically verified, severely symptomatic endometriosis and two of the patients also with high-grade serous carcinoma.

resultsWhole-exome sequencing revealed three rare candidate predisposing variants segregating with endometriosis. The variants were c.1238C>T, p.(Pro413Leu) in FGFR4, c.5065C>T, p.(Arg1689Trp) in NALCN, and c.2086G>A, p.(Val696Met) in NAV2. The only variant predicted deleterious by in silico tools was the one in FGFR4. Further screening of the variants in 92 Finnish endometriosis and in 19 endometriosis-ovarian cancer patients did not reveal additional carriers. Histopathology, positive p53 immunostaining, and genetic analysis supported the high-grade serous subtype of the two tumors in the family.

conclusionsHere, we provide FGFR4, NALCN, and NAV2 as novel high-risk candidate genes for familial endometriosis. Our results also support the association of endometriosis with high-grade serous carcinoma. Further studies are required to validate the findings and to reveal the exact pathogenesis mechanisms of endometriosis. Elucidating the genetic background of endometriosis defines the etiology of the disease and provides opportunities for expedited diagnostics and personalized treatments.

Indexed as

CarcinomaEndometriosisOvarian NeoplasmsAgedExome SequencingFemaleGenetic Predisposition to DiseaseHumansCandidate genesEndometriosisFamilial predispositionFGFR4High-grade serous carcinomaNALCNNAV2Whole-exome sequencing

Identifiers

PMID37789421
PMCPMC10546785
OpenAlexW4387309745

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.