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1. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Author

Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, 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, Noukas, 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-Gorska, 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, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, Zondervan, KT, Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, 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, Noukas, 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-Gorska, 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, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, and Zondervan, KT

Abstract

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.

Published
2023

2. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Author

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, 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, 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, and Zondervan KT

Subjects
Female, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, Pain, Comorbidity, Endometriosis genetics, Endometriosis metabolism
Abstract

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., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2023
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3. Binding of CXCL8/IL-8 to Mycobacterium tuberculosis Modulates the Innate Immune Response.

Author

Krupa A, Fol M, Dziadek BR, Kepka E, Wojciechowska D, Brzostek A, Torzewska A, Dziadek J, Baughman RP, Griffith D, and Kurdowska AK

Subjects
Bronchoalveolar Lavage Fluid immunology, Humans, Immunity, Innate, Interleukin-8 analysis, Lung immunology, Phagocytosis, Interleukin-8 physiology, Mycobacterium tuberculosis immunology
Abstract

Interleukin-8 (IL-8) has been implicated in the pathogenesis of several human respiratory diseases, including tuberculosis (TB). Importantly and in direct relevance to the objectives of this report quite a few findings suggest that the presence of IL-8 may be beneficial for the host. IL-8 may aid with mounting an adequate response during infection with Mycobacterium tuberculosis (M. tb); however, the underlying mechanism remains largely unknown. The major goal of our study was to investigate the contribution of IL-8 to the inflammatory processes that are typically elicited in patients with TB. We have shown for the first time that IL-8 can directly bind to tubercle bacilli. We have also demonstrated that association of IL-8 with M. tb molecules leads to the augmentation of the ability of leukocytes (neutrophils and macrophages) to phagocyte and kill these bacilli. In addition, we have shown that significant amount of IL-8 present in the blood of TB patients associates with erythrocytes. Finally, we have noted that IL-8 is the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and CD8(+) T cells). In summary, our data suggest that the association of IL-8 with M. tb molecules may modify and possibly enhance the innate immune response in patients with TB.

Published
2015
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