The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
Nilufer RahmiogluSally MortlockMarzieh GhiasiPeter Loof MøllerLilja StefansdottirGeneviève GalarneauConstance TurmanRebecca DanningMatthew H LawYadav SapkotaParaskevi ChristofidouSini SkarpAyush GiriKarina BanasikMichal KrassowskiMaarja LepametsBłażej MarciniakMargit NõukasDanielle PerroEeva SlizMarta Sobalska-KwapisGudmar ThorleifssonNura Fitnat Topbas SelcukiAllison VitonisDavid WestergaardRagnheidur ArnadottirKristoffer S BurgdorfArchie I CampbellCecilia S K CheukCaterina ClementiJames CookImmaculata De VivoAmy DiVastaO DorienJacqueline F DonoghueTodd L EdwardsPierre FontanillasJenny N FungReynir Tomas GeirssonJane E GirlingPaivi HarkkiHolly R HarrisMartin HealeyOskari HeikinheimoSarah Holdsworth-CarsonIsabel Charlotte HostettlerHenry HouldenSahar HoushdaranJuan C IrwinMarjo-Riitta JarvelinYoichiro KamataniStephen H KennedyEwa KepkaJohannes KettunenMichiaki KuboBartosz KuligVenla KurraFinnpec Hannele LaivuoriMarc R LauferCecilia M LindgrenStuart MacGregorMassimo ManginoNicholas G MartinCharoula MatalliotakiMichail MatalliotakisAlison D MurrayAnne NdunguCamran NezhatCatherine M OlsenJessica Opoku-AnaneSandosh PadmanabhanManish ParanjpeMaire PetersGrzegorz PolakDavid J PorteousJoseph RabbanKathyrn M RexrodeHanna RomanowiczMerli SaareLiisu SaavalainenAndrew J SchorkSushmita SenAmy L ShafrirAnna Siewierska-GórskaMarcin SłomkaBlair Hamilton SmithBeata SmolarzTomasz SzaflikKrzysztof SzyłłoAtsushi TakahashiKathryn L TerryCarla TomassettiSusan A TreloarArne VanhieKaty VincentKim C VoDavid John WerringEleftheria ZegginiMaria I Zervounull nullnull nullnull nullnull nullnull nullSosuke AdachiJulie E BuringPaul M RidkerThomas D'HoogheGeorge N GoulielmosDharani K HapangamaCaroline HaywardAndrew W HorneSiew-Kee Amanda LowHannu MartikainenDaniel I ChasmanPeter A W RogersPhilippa T SaundersMarina SirotaTimothy D SpectorDominik StrapagielJoyce Y TungDavid C WhitemanLinda C GiudiceDigna R Velez-EdwardsOuti UimariPeter KraftAndres SalumetsDale R NyholtReedik MägiKári StefánssonChristian M BeckerPiraye Yurttas-BeimValgerdur SteinthorsdottirMette NygaardStacey A MissmerGrant W MontgomeryAndrew P MorrisKrina T ZondervanPublished in: Nature genetics (2023)
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.
Keyphrases
- chronic pain
- genome wide
- pain management
- copy number
- dna methylation
- neuropathic pain
- systematic review
- genome wide association study
- randomized controlled trial
- poor prognosis
- transcription factor
- oxidative stress
- gene expression
- rectal cancer
- cancer therapy
- spinal cord injury
- long non coding rna
- lung function
- drug delivery
- binding protein
- insulin resistance
- skeletal muscle
- growth factor
- genome wide association