biostudies-literatureUnknown5(1)Ruotsalainen SECardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland's population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In a large Finnish biobank study FinnGen, we identified an association between an inframe insertion rs534125149 in MFGE8 (encoding lactadherin) and protection against coronary atherosclerosis. TCommunications biology802https://www.ebi.ac.uk/biostudies/studies/S-EPMC9385630biostudies-literatureInframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis.PMC9385630Lahteenmaki SHelminen MKaprio JBiswas SHu XHarju THunkapiller JObeidat MESmaoui NPendergrass SJohn SBlomster TArvas MFinnGende Lange KSoini SVahatalo IPihlajamaki JSiegel RBing NLaitinen TYamanashi YGracia-Tabuenca JAddis LBowers NMatsuda KBaird DKamatani YAbbasi AZiemann AEsko TMeretoja TMorisaki TKalliala IBrein GMilani LChhibber AXu FXu EXu HJoensuu HMishra BHSuominen LKoretsune YUsiskin KFurukawa YSiirtola HMohammed ECummings BSoininen HTachmazidou IMehtonen JTuomi TOllila TKarihtala PMiller MDaly MJRathinakannan VSSipila KEhm MRipatti SRiley-Gills BMiller RDavis JWUimari OTurunen JAGursoy UAuge FDonner KMustaniemi LWiden EHuertas-Vazquez AQuarless DSchleutker JMurayama SHiekkalinna TKettunen JWadhawan SMishra RWong RHeikinheimo OMishra PPUusitalo-Jarvinen HGanna AYamaji KGreenberg SChung JHochfeld MSalminen AGhosh SRajpal DGossel MNeduva VKristiansson KTian RKotaniemi-Talonen LElenius KPopovic RLoukola APerola MReeve MPJarvensivu ERemes AEkholm ETuovila OWaring JKoskelainen SBrauer MMantyla PTsuo KRaghavan NHedman AHassan SKilpelainen EPaajanen TPalin KParkkinen JChen CYJacob JCrohns MBetts JMakikallio KKoskela JChen XKauppila SJacob HPaul DPelkonen MKulkarni DMagi RRaipal DHakanen AHavulinna AGormley PKahonen MChen HMasumoto ATienari PKing KSTasanen KEsmaeeli SAuvinen PKuopio TRinne JTsai ETeng ERaivio MKujala UKaarniranta KNagai AValimaki NLoboda APodgornaia AAsai SVirolainen PLiu JSuzuki TPlenge RLiu MChallis BRivas MPylkas KObata DMaasha MYoshimori KKlinger KMannikko LSchutzman JNagayama SUusitalo HMantere TPalomaki AAnttonen VGhazal AStrauss EMurakami YDella Briotta Parolo PKvikstad EMetspalu ARueger SSipila TPParn KKallio LAuro KHeyne HLuukkaala THinttala Rvan Adelsberg JCall KSinisalo JMannermaa ALiu DLuo SJulkunen VKangasniemi EPunkka EFarkkila MKivinen KSinozaki NDaly MLemmela SNieminen KLahesmaa RPulford DPalotie ASoylemez OLassi GSistonen TMars NLaivuori HHigashiyama MFleuren WFox CVaura FHuilaja LLaakkonen EKalpala KMcCarthy MMakela JClose DPalotie UAoxing LMcCarthy LRaitakari OPartanen JLertratanakul AAaltonen LLaiho PKanai MMakela TLaukkanen MJuonala MXia THLaukkanen JSeitsonen SLaakso MMattson JRice DPirila LIsomaki PPolo PJussila AKrebs KPakkanen RCole ARunz HSalomaa VLee JAaltonen VShen HYSalo TCaliskan MChu ASerpi RBhangale THeron SLoomis SChang DJyrhama TKurra VMaranville JKalaoja MKilpi TBehrens TMcDonough SLahtela LENiemi MEKaunisto MSurakka IRuotsalainen SEHuhtakangas JKarjalainen MKarjalainen JJalanko AVaarasmaki MPitkaranta AZhou WEklund KRamo JNelis MMalarstig APeltonen SHuang YHautalahti MMitchell AChatelain CRenaud NNieminen PTukiainen TAavikko MShkura KPitkanen EKosma VMDada OAJunttila JKankaanranta HSun BWang CVuoti SHautala NPeltola JLinden KPikkarainen SRahimov FMackay ALlorens VSoutherington TKoivusalo MNiiranen TMetsarinne KElliott AWu YPitkanen NKurki MEaton SMuto KObara WGordillo JERitari JBiobank Japan ProjectHeap GTaskinen MRHeikkinen SVoutilainen MBronson PRiley-Gillis BZierer JGraham SGraham RHiltunen MSinha VEicher JLuodonpaa MKiiskinen TLu TYang RHannula-Jouppi KPetrovski SWigmore EKauppi PGordin DSiponen MKaukinen KAuranen ALehtonen ALahdenpera STuppurainen MTakahashi YChoy DLehisto AShcherban AMorin-Papunen LEstonian Biobank Research TeamLehtonen HMinami SCarpen OHyvarinen KYamaguchi HWaterworth DTakahashi KSalmi TKaipiainen-Seppanen OJambulingam DLehtimaki TKiviniemi MKaiharju EKalviainen RKoulu LRuotsalainen SKoskinen MKajanne ROkada YSmith SKumar JPalta POh DKallionpaa RPussinen PGarcia-Tabuenca JMattsson HfalseInframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis.Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland's population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In a large Finnish biobank study FinnGen, we identified an association between an inframe insertion rs534125149 in MFGE8 (encoding lactadherin) and protection against coronary atherosclerosis. T2022-01-01T00:00:00Z2022 Aug2026-05-09T19:35:40.008Z2024-11-20T11:19:21.934ZS-EPMC93856303597813310.1038/s42003-022-03552-0