biostudies-literatureMueller SHIntramural NIH HHSCancer Research UKWorld Health OrganizationEuropean Research CouncilNCCDPHP CDC HHSFIC NIH HHSNIEHS NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)NCI NIH HHSCancer Foundation Finland srWellcome Trust7https://www.ebi.ac.uk/biostudies/studies/S-EPMC9878779biostudies-literatureUnknown15(1)<h4>Background</h4>Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.<h4>Methods</h4>We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.<h4>Results</h4>In European ancestry samples, 14 genGenome medicineAggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.PMC9878779C5047/A106921000143U19 CA148537U01 CA176726C12292/A11174C1287/A10118C1281/A12014U01 CA179715C1287/A10710HDR-900329186K24 CA169004R01 CA120120NU58DP006344U19 CA14806514136R35 CA253187U54 CA156733C1275/C22524P50 CA125183G1000143Z01 ES049030D43 TW009112C8221/A19170HHSN261201800009IZ01 ES04903316563C490/A16561948561P30 CA033572R01 CA176785P30 ES010126C1275/A11699203477/Z/16/ZU01 CA199277R01 CA148667001P50 CA058223MR/M012190/1220031Z01 CP010119C570/A16491C1275/A19187UM1 CA186107PGFAR 0707-10031P30 CA008748C1287/A16563C8197/A1656510118HHSN261201800032IR01 CA116167DRCPGM\100071UM1 CA164920P30 CA023100U01 CA164920R01 CA077398UM1 CA164917C1275/A15956C490/A10124R01 CA100374HHSN261201800015IR01 CA192393C5047/A8384UM1 CA176726R03 CA130065IS-BRC-1215-20007U19 CA148112C5047/A15007Z01 ES044005MC_UU_00004/01Mavroudis DTaylor JAPatel ANBCS CollaboratorsPerou CMAhearn TUTollenaar RAEMLe Marchand LEaston DFHoppe RWolk ALo WYTeras LRReinertsen KVFletcher OJones MEKitahara CMShen CYRack BOlopade OIHarrington PAHall PHooning MJSchmutzler RKGenkinger JHarkness EFMarsh DAbu-Ful ZLush MHein AVijai JDwek MHo WKRiis MZiv EGarcia-Saenz JAHolmen MMBojesen SEPlaseska-Karanfilska DRamachandran DBogdanova NVTorres-Mejia GDaly MBJohn EMManoochehri MYamaji THaakensen VAntonenkova NNAugustinsson ASachchithananthan MEccles DMFossa ALambrechts DRennert GYip DWu AHKuchenbaecker KBDossus LBaert TKim SWGarcia-Closas MKubelka-Sabit KToland AEEngebraten OOlsson HOffit KGuenel PPharoah PDPMueller SHHemingway HEvans DGSimard JDavis AChanock SJHartikainen JMLi JSharma PChan TLHahnen EHuo DHowell AFasching PAKwong ATeo SHSchmidt MKNevanlinna HMichailidou KHoulston RSRuddy KJScott CKaresen RLinet MABCTB InvestigatorsHunter DJMenon URadice PTroester MAScott RGao YTMuir KHaiman CAPatel AVRomero ARuebner MDennis JSawyer EJHelland ACastelao JEJakubowska AHartman MMannermaa AShah MSchlichting EFlyger HO'Brien KMDork TObi NKiserud CEKoutros SBlomqvist CBrucker SYGentry-Maharaj ABaxter RSahlberg KKSauer TEkici ABValkovskaya MWendt CGundert MZheng WKhusnutdinova EKPeto JBrenner HTruong TWinqvist RLacey JVKaaks RHakansson NMurphy RAChung WKBenitez JEngel CBonanni BYang XRTorres DKurian AWBehrens SNiederacher DSurowy HZiogas ALai AGGago-Dominguez MJung AOttestad LBuys SSSimpson PDunning AMRashid MUAndrulis ILYu JCKristensen VNMatsuo KLophatananon ACarpenter JWeinberg CRWang QKang DIto HCouch FJTapper WJBolla MKChang-Claude JGraham DAronson KJFreeman LEBCTS ConsortiumOlshan AFCornelissen SColonna SVArndt VKraft PSaloustros EGrassmann FAnton-Culver HVachon CMGeisler JLong JPresneau NBeckmann MWDevilee PTamimi RMBorresen-Dale ALIwasaki MPark SKSchneider MOCzene KMargolin SShu XOHaeberle LNewman WGSandler DPGrenaker Alnaes GIEliassen AHHopper JLNaume BChoi JYBermisheva MHamann UJanni WPathmanathan NfalseAggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.<h4>Background</h4>Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.<h4>Methods</h4>We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.<h4>Results</h4>In European ancestry samples, 14 gen2023-01-01T00:00:00Z2023 Jan2026-07-14T21:10:43.539Z2026-06-24T03:11:19.037ZS-EPMC98787793670316410.1186/s13073-022-01152-5