The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
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 M-R., 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., Słomka M., Smith BH., Smolarz B., Szaflik T., Szyłło 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 S-K., 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.
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.