{"id":"https://openalex.org/W7207846434","doi":"https://doi.org/10.64898/2026.08.31.26361798","title":"Hybrid risk scores integrating polygenic and clinical variables for endometriosis prediction","display_name":"Hybrid risk scores integrating polygenic and clinical variables for endometriosis prediction","publication_year":2026,"publication_date":"2026-09-03","ids":{"openalex":"https://openalex.org/W7207846434","doi":"https://doi.org/10.64898/2026.08.31.26361798"},"language":"en","primary_location":{"id":"doi:10.64898/2026.08.31.26361798","doi":"https://doi.org/10.64898/2026.08.31.26361798","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.31.26361798","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/03/2026.08.31.26361798.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/03/2026.08.31.26361798.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5004404021","display_name":"Oksana Goroshchuk","orcid":"https://orcid.org/0000-0002-1585-1962","observed_orcids":["https://orcid.org/0000-0002-1585-1962"]},"institutions":[{"id":"https://openalex.org/I123387679","display_name":"Uppsala University","ror":"https://ror.org/048a87296","country_code":"SE","type":"education","lineage":["https://openalex.org/I123387679"]},{"id":"https://openalex.org/I28166907","display_name":"Karolinska Institutet","ror":"https://ror.org/056d84691","country_code":"SE","type":"education","lineage":["https://openalex.org/I28166907"]},{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["SE","US"],"is_corresponding":false,"raw_author_name":"Oksana Goroshchuk","raw_affiliation_strings":["Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden","Department of Neurology, Yale School of Medicine, New Haven, CT, USA","Department of Women\u2019s and Children\u2019s Health, Uppsala University, Uppsala, Sweden"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden","institution_ids":["https://openalex.org/I28166907"]},{"raw_affiliation_string":"Department of Neurology, Yale School of Medicine, New Haven, CT, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Department of Women\u2019s and Children\u2019s Health, Uppsala University, Uppsala, Sweden","institution_ids":["https://openalex.org/I123387679"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5044784338","display_name":"D\u00f3ra Koller","orcid":"https://orcid.org/0000-0002-0415-0466","observed_orcids":["https://orcid.org/0000-0002-0415-0466"]},"institutions":[{"id":"https://openalex.org/I2801357902","display_name":"Instituto de Salud Carlos III","ror":"https://ror.org/00ca2c886","country_code":"ES","type":"nonprofit","lineage":["https://openalex.org/I2801357902","https://openalex.org/I4387152914"]},{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]},{"id":"https://openalex.org/I4387155026","display_name":"Institut de Recerca Sant Pau","ror":"https://ror.org/005teat46","country_code":"ES","type":"healthcare","lineage":["https://openalex.org/I4387153040","https://openalex.org/I4387155026"]},{"id":"https://openalex.org/I4405279361","display_name":"Red de Salud Materno Infantil y del Desarrollo","ror":"https://ror.org/01bvq8z75","country_code":"ES","type":"facility","lineage":["https://openalex.org/I4405279361"]}],"countries":["ES","US"],"is_corresponding":true,"raw_author_name":"Dora Koller","raw_affiliation_strings":["Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA","Spanish Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24/0013/0001) Instituto de Salud Carlos III, Madrid, Spain","Women and Perinatal Health Research Group, Institut de Recerca (IR) Sant Pau, Barcelona, Spain"],"raw_orcid":"https://orcid.org/0000-0002-0415-0466","affiliations":[{"raw_affiliation_string":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Spanish Network in Maternal, Neonatal, Child and Developmental Health Research (RICORS-SAMID, RD24/0013/0001) Instituto de Salud Carlos III, Madrid, Spain","institution_ids":["https://openalex.org/I2801357902","https://openalex.org/I4405279361"]},{"raw_affiliation_string":"Women and Perinatal Health Research Group, Institut de Recerca (IR) Sant Pau, Barcelona, Spain","institution_ids":["https://openalex.org/I4387155026"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":6,"corresponding_author_ids":["https://openalex.org/A5044784338"],"corresponding_institution_ids":["https://openalex.org/I2801357902","https://openalex.org/I32971472","https://openalex.org/I4387155026","https://openalex.org/I4405279361"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10935","display_name":"Endometriosis Research and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10935","display_name":"Endometriosis Research and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12096","display_name":"Ectopic Pregnancy Diagnosis and Management","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/endometriosis","display_name":"endometriosis","score":0.9950000047683716},{"id":"https://openalex.org/keywords/polygenic-risk-score","display_name":"polygenic risk score","score":0.9869999885559082},{"id":"https://openalex.org/keywords/comorbidity","display_name":"comorbidities","score":0.9070000052452087},{"id":"https://openalex.org/keywords/all-of-us-research-program","display_name":"All of Us","score":0.8100000023841858},{"id":"https://openalex.org/keywords/xgboost","display_name":"XGBoost","score":0.800000011920929},{"id":"https://openalex.org/keywords/random-forest","display_name":"random forest","score":0.6430000066757202},{"id":"https://openalex.org/keywords/logistic-regression","display_name":"logistic regression","score":0.8209999799728394},{"id":"https://openalex.org/keywords/delayed-diagnosis","display_name":"delayed diagnosis","score":0.640999972820282},{"id":"https://openalex.org/keywords/genetic-ancestry","display_name":"genetic ancestry","score":0.4690000116825104},{"id":"https://openalex.org/keywords/reproductive-factors","display_name":"reproductive factors","score":0.5},{"id":"https://openalex.org/keywords/environmental-risk-factors","display_name":"environmental risk factors","score":0.6159999966621399}],"concepts":[{"id":"https://openalex.org/C151956035","wikidata":"https://www.wikidata.org/wiki/Q1132755","display_name":"Logistic regression","level":2,"score":0.6990000009536743},{"id":"https://openalex.org/C2779522080","wikidata":"https://www.wikidata.org/wiki/Q205764","display_name":"Endometriosis","level":2,"score":0.6818000078201294},{"id":"https://openalex.org/C2779159551","wikidata":"https://www.wikidata.org/wiki/Q1414874","display_name":"Comorbidity","level":2,"score":0.6363999843597412},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5670999884605408},{"id":"https://openalex.org/C184898388","wikidata":"https://www.wikidata.org/wiki/Q1435712","display_name":"Pairwise comparison","level":2,"score":0.44269999861717224},{"id":"https://openalex.org/C27438332","wikidata":"https://www.wikidata.org/wiki/Q2873","display_name":"Principal component analysis","level":2,"score":0.4194999933242798},{"id":"https://openalex.org/C2993137441","wikidata":"https://www.wikidata.org/wiki/Q28135712","display_name":"Polygenic risk score","level":5,"score":0.41370001435279846},{"id":"https://openalex.org/C127808970","wikidata":"https://www.wikidata.org/wiki/Q385989","display_name":"Bonferroni correction","level":2,"score":0.37209999561309814},{"id":"https://openalex.org/C119043178","wikidata":"https://www.wikidata.org/wiki/Q320723","display_name":"Covariate","level":2,"score":0.3659000098705292},{"id":"https://openalex.org/C169258074","wikidata":"https://www.wikidata.org/wiki/Q245748","display_name":"Random forest","level":2,"score":0.3564999997615814},{"id":"https://openalex.org/C177264268","wikidata":"https://www.wikidata.org/wiki/Q1514741","display_name":"Set (abstract data type)","level":2,"score":0.3310999870300293},{"id":"https://openalex.org/C168743327","wikidata":"https://www.wikidata.org/wiki/Q1826427","display_name":"Random effects model","level":3,"score":0.3215999901294708},{"id":"https://openalex.org/C117220453","wikidata":"https://www.wikidata.org/wiki/Q5172842","display_name":"Correlation","level":2,"score":0.3131999969482422},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.3118000030517578},{"id":"https://openalex.org/C138528620","wikidata":"https://www.wikidata.org/wiki/Q2510752","display_name":"Explained variation","level":2,"score":0.303600013256073},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.29580000042915344},{"id":"https://openalex.org/C58489278","wikidata":"https://www.wikidata.org/wiki/Q1172284","display_name":"Data set","level":2,"score":0.29420000314712524},{"id":"https://openalex.org/C170964787","wikidata":"https://www.wikidata.org/wiki/Q7611170","display_name":"Stepwise regression","level":2,"score":0.28200000524520874},{"id":"https://openalex.org/C45804977","wikidata":"https://www.wikidata.org/wiki/Q7239673","display_name":"Predictive modelling","level":2,"score":0.2752000093460083},{"id":"https://openalex.org/C21308566","wikidata":"https://www.wikidata.org/wiki/Q7169365","display_name":"Permutation (music)","level":2,"score":0.2727999985218048},{"id":"https://openalex.org/C44249647","wikidata":"https://www.wikidata.org/wiki/Q208498","display_name":"Confidence interval","level":2,"score":0.2660999894142151},{"id":"https://openalex.org/C58471807","wikidata":"https://www.wikidata.org/wiki/Q327120","display_name":"Receiver operating characteristic","level":2,"score":0.25690001249313354},{"id":"https://openalex.org/C83546350","wikidata":"https://www.wikidata.org/wiki/Q1139051","display_name":"Regression","level":2,"score":0.25540000200271606},{"id":"https://openalex.org/C183905921","wikidata":"https://www.wikidata.org/wiki/Q1038757","display_name":"Multiple comparisons problem","level":2,"score":0.2533999979496002},{"id":"https://openalex.org/C152877465","wikidata":"https://www.wikidata.org/wiki/Q208042","display_name":"Regression analysis","level":2,"score":0.25029999017715454}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.08.31.26361798","doi":"https://doi.org/10.64898/2026.08.31.26361798","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.31.26361798","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/03/2026.08.31.26361798.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.08.31.26361798","doi":"https://doi.org/10.64898/2026.08.31.26361798","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.31.26361798","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/03/2026.08.31.26361798.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.98580002784729,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2604507767","display_name":"Research Matters: Creating Possibilities to Achieve Health and Wellness for All of Us Research Program","funder_award_id":"OT2OD025337","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G2880245766","display_name":null,"funder_award_id":"RYC2024-050099-I","funder_id":"https://openalex.org/F4320322930","funder_display_name":"Ministerio de Ciencia e Innovaci\u00f3n"},{"id":"https://openalex.org/G402197978","display_name":"Precision Medicine Initiative Cohort Program Biobank","funder_award_id":"U24OD023121","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5248101980","display_name":"Technology to Empower Changes in Health (TECH) Network Participant Technologies Center","funder_award_id":"U24OD023176","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G6129883062","display_name":"Data and Research Support Center ","funder_award_id":"U2COD023196","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G7835049221","display_name":"Adaptive Platform for Personalized Engagement","funder_award_id":"U24OD023163","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G966751541","display_name":"PRIDEnet for the All of Us Research Program ","funder_award_id":"OT2OD025276","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"}],"funders":[{"id":"https://openalex.org/F4320322930","display_name":"Ministerio de Ciencia e Innovaci\u00f3n","ror":null},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7207846434.pdf","grobid_xml":"https://content.openalex.org/works/W7207846434.grobid-xml"},"referenced_works_count":24,"referenced_works":["https://openalex.org/W1908598451","https://openalex.org/W2099085143","https://openalex.org/W2761276004","https://openalex.org/W2913997948","https://openalex.org/W2951553270","https://openalex.org/W3107844184","https://openalex.org/W3119380823","https://openalex.org/W3134885188","https://openalex.org/W3193423663","https://openalex.org/W4205170775","https://openalex.org/W4234160457","https://openalex.org/W4284891101","https://openalex.org/W4324045019","https://openalex.org/W4362554931","https://openalex.org/W4386410410","https://openalex.org/W4388572510","https://openalex.org/W4391925485","https://openalex.org/W4410333869","https://openalex.org/W4412790739","https://openalex.org/W4413985078","https://openalex.org/W4416679389","https://openalex.org/W7125682816","https://openalex.org/W7158935736","https://openalex.org/W7166874846"],"related_works":["https://openalex.org/W7161166668","https://openalex.org/W4200341102","https://openalex.org/W4281695341","https://openalex.org/W4414148610","https://openalex.org/W7165549801","https://openalex.org/W4392355862","https://openalex.org/W6902044604","https://openalex.org/W6920992802","https://openalex.org/W7128543540","https://openalex.org/W3019844658"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Endometriosis":[2],"affects":[3],"approximately":[4],"10%":[5],"of":[6,87,312,323],"reproductive-age":[7],"women":[8],"and":[9,16,56,66,78,126,133,141,147,157,174,185,224,232,254,262,279,295,320,329,336],"is":[10],"associated":[11],"with":[12,36,53,76,177,198,293],"substantial":[13],"diagnostic":[14],"delay":[15],"heterogeneous":[17],"symptom":[18,57,79,146,223,294],"presentation.":[19],"Prior":[20],"machine-learning":[21],"prediction":[22,326],"models":[23,70,128],"have":[24],"relied":[25],"on":[26,31,270],"comorbidity":[27,148,225,296],"data":[28,58,80,297],"alone":[29,257],"or":[30,38],"small":[32],"candidatevariant":[33],"genetic":[34,135,253],"scores,":[35],"inconsistent":[37],"incompletely":[39],"reported":[40],"performance.":[41],"No":[42],"study":[43,315],"has":[44],"combined":[45,154],"a":[46,60,72,170,199,286,305,310],"well-powered,":[47,306],"multi-ancestry":[48,74,118,307],"polygenic":[49],"risk":[50],"score":[51],"(PRS)":[52],"environmental,":[54],"reproductive,":[55],"in":[59,83,169,246],"single":[61],"hybrid":[62,68,324],"model.":[63],"We":[64],"developed":[65],"evaluated":[67],"risk-prediction":[69],"integrating":[71],"genome-wide,":[73],"PRS":[75,109,158,236,263,292,308],"clinical":[77],"for":[81,182,216,327],"endometriosis":[82,96,328],"the":[84,217,239,291,299,318],"US-based":[85],"All":[86],"Us":[88],"Research":[89],"Program.":[90],"Methods":[91],"Among":[92],"69,376":[93],"participants":[94],"(15,382":[95],"cases,":[97],"53,994":[98],"controls)":[99],"across":[100],"six":[101],"genetically":[102],"inferred":[103],"ancestry":[104],"groups,":[105],"we":[106],"computed":[107],"individual-level":[108],"values":[110],"using":[111],"PRS-CS":[112],"weights":[113],"derived":[114],"from":[115,206],"an":[116],"independent,":[117],"GWAS.":[119],"Five":[120],"nested":[121],"logistic":[122,230],"regression,":[123],"random":[124,233],"forest,":[125],"XGBoost":[127,227],"progressively":[129],"added":[130],"age,":[131,210,251],"ancestry,":[132,211],"within-ancestry":[134],"principal":[136,212],"components":[137],"(Model":[138,144,150,155,162],"1),":[139],"environmental":[140,271],"reproductive":[142],"factors":[143,272],"2),":[145],"indicators":[149],"3),":[151],"all":[152],"covariates":[153],"4),":[156],"\u00d7":[159,264],"environment":[160,265],"interactions":[161,266],"5).":[163],"Performance":[164],"was":[165],"assessed":[166],"by":[167,222,243],"AUROC":[168,194,207],"held-out":[171],"test":[172],"set":[173],"5-fold":[175],"cross-validation,":[176],"class-weighted,":[178],"Youden-optimized":[179],"thresholds":[180],"used":[181],"sensitivity,":[183],"specificity,":[184],"predictive":[186],"values;":[187],"permutation":[188,244],"importance":[189,245],"identified":[190],"top":[191,240],"contributors.":[192],"Pairwise":[193],"differences":[195],"were":[196],"tested":[197],"Holm-corrected":[200],"DeLong-type":[201],"test.":[202],"Results":[203],"Discrimination":[204],"improved":[205],"0.63":[208],"(PRS,":[209],"components)":[213],"to":[214,303,331],"0.72":[215],"full":[218],"model,":[219,249],"driven":[220],"mainly":[221],"data.":[226],"consistently":[228],"outperformed":[229],"regression":[231],"forest.":[234],"The":[235],"ranked":[237],"among":[238],"individual":[241],"predictors":[242],"nearly":[247],"every":[248],"alongside":[250],"while":[252],"demographic":[255],"information":[256],"gave":[258,298],"only":[259],"modest":[260],"discrimination,":[261],"did":[267],"not":[268],"improve":[269],"alone.":[273],"Threshold":[274],"optimization":[275],"yielded":[276],"balanced":[277],"sensitivity":[278,284],"specificity":[280],"(~0.67/0.65)":[281],"versus":[282],"near-zero":[283],"at":[285],"default":[287],"threshold.":[288],"Conclusions":[289],"Combining":[290],"best":[300],"discrimination":[301],"compared":[302],"solely":[304],"as":[309,339],"predictor":[311],"endometriosis.":[313],"This":[314],"clarifies":[316],"both":[317],"promise":[319],"current":[321],"limits":[322],"genetic-clinical":[325],"points":[330],"symptom-based":[332],"phenotyping,":[333],"molecular":[334],"subtyping,":[335],"external":[337],"validation":[338],"priorities.":[340]},"counts_by_year":[],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2026-09-04T00:00:00"}