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 g...
| Authors | Rahmioglu, N; Mortlock, S; Ghiasi, M; Møller, PL; Stefansdottir, L; Galarneau, G; Turman, C; Danning, R; Law, MH; Sapkota, Y; Christofidou, P; Skarp, S; Giri, A; Banasik, K; Krassowski, M; Lepamets, M; Marciniak, B; Nõukas, M; Perro, D; Sliz, E; Sobalska-Kwapis, M; Thorleifsson, G; Topbas-Selcuki, NF; Vitonis, A; Westergaard, D; Arnadottir, R; Burgdorf, KS; Campbell, A; Cheuk, CSK; Clementi, C; Cook, J; De Vivo, I; DiVasta, A; Dorien, O; Donoghue, JF; Edwards, T; Fontanillas, P; Fung, JN; Geirsson, RT; Girling, JE; Harkki, P; Harris, HR; Healey, M; Heikinheimo, O; Holdsworth-Carson, S; Hostettler, IC; Houlden, H; Houshdaran, S; Irwin, JC; Jarvelin, MR; Kamatani, Y; Kennedy, SH; Kepka, E; Kettunen, J; Kubo, M; Kulig, B; Kurra, V; Laivuori, H; Laufer, MR; Lindgren, CM; MacGregor, S; Mangino, M; Martin, NG; Matalliotaki, C; Matalliotakis, M; Murray, AD; Ndungu, A; Nezhat, C; Olsen, CM; Opoku-Anane, J; Padmanabhan, S; Paranjpe, M; Peters, M; Polak, G; Porteous, DJ; Rabban, J; Rexrode, KM; Romanowicz, H; Saare, M; Saavalainen, L; Schork, AJ; Sen, S; Shafrir, AL; Siewierska-Górska, A; Slomka, M; Smith, BH; Smolarz, B; Szaflik, T; Szyllo, K; Takahashi, A; Terry, KL; Tomassetti, C; Treloar, SA; Vanhie, A; Vincent, K; Vo, KC; Werring, DJ; Zeggini, E; Zervou, MI; DBDS Genomic Consortium; FinnGen Study; FinnGen Endometriosis Taskforce; Celmatix Research Team; 23andMe Research Team; Adachi, S; Buring, JE; Ridker, PM; D'Hooghe, T; Goulielmos, GN; Hapangama, DK; Hayward, C; Horne, AW; Low, SK; Martikainen, H; Chasman, DI; Rogers, PAW; Saunders, PT; Sirota, M; Spector, T; Strapagiel, D; Tung, JY; Whiteman, DC; Giudice, LC; Velez-Edwards, DR; Uimari, O; Kraft, P; Salumets, A; Nyholt, DR; Mägi, R; Stefansson, K; Becker, CM; Yurttas-Beim, P; Steinthorsdottir, V; Nyegaard, M; Missmer, SA; Montgomery, GW; Morris, AP; Zondervan, KT |
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| Journal | NATURE GENETICS |
| Pages | 423-436 |
| Volume | 55 |
| Date | 13/04/2023 |
| Grant ID | P50 HD104224 | NICHD NIH HHS [HD] (United States); UM1 CA176726 | NCI NIH HHS [CA] (United States); R01 HD094842 | NICHD NIH HHS [HD] (United States); R01 HD096033 | NICHD NIH HHS [HD] (United States); UM1 CA186107 | NCI NIH HHS [CA] (United States); MR/K011480/1 | Medical Research Council [MRC_] (United Kingdom); R01 HD089511 | NICHD NIH HHS [HD] (United States); Wellcome Trust [WT_] (United Kingdom); R21 HD096358 | NICHD NIH HHS [HD] (United States); MC_UU_00007/10 | Medical Research Council [MRC_] (United Kingdom); 084766 | Wellcome Trust [WT_] (United Kingdom) |
| Funding Body | |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41588-023-01323-z |