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Cited by 198

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection

Open access
Zekavat, Seyedeh M., Lin, Shu-Hong, Bick, Alexander G., Liu, Aoxing, Paruchuri, Kaavya, Wang, Chen, Uddin, Md Mesbah, Ye, Yixuan, Yu, Zhaolong, Liu, Xiaoxi, Kamatani, Yoichiro, Bhattacharya, Romit, Pirruccello, James P., Pampana, Akhil, Loh, Po-Ru, Kohli, Puja, McCarroll, Steven A., Kiryluk, Krzysztof, Neale, Benjamin, Ionita-Laza, Iuliana, Engels, Eric A., Brown, Derek W., Smoller, Jordan W., Green, Robert, Karlson, Elizabeth W., Lebo, Matthew, Ellinor, Patrick T., Weiss, Scott T., Daly, Mark J., The Biobank Japan Project, Koyama, Satoshi, Ito, Kaoru, Momozawa, Yukihide, Matsuda, Koichi, Yamanashi, Yuji, Furukawa, Yoichi, Morisaki, Takayuki, Murakami, Yoshinori, Muto, Kaori, Nagai, Akiko, Obara, Wataru, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Suzuki, Takao, Sinozaki, Nobuaki, Yamaguchi, Hiroki, Minami, Shiro, Murayama, Shigeo, Yoshimori, Kozo, Nagayama, Satoshi, Obata, Daisuke, Higashiyama, Masahiko, Masumoto, Akihide, Koretsune, Yukihiro, FinnGen Consortium, Palotie, Aarno, Ziemann, Adam, Mitchell, Adele, Huertas-Vazquez, Adriana, Salminen, Aino, Jussila, Airi, Havulinna, Aki, Mackay, Alex, Abbasi, Ali, Elliott, Amanda, Cole, Amy, Shcherban, Anastasia, Mälarstig, Anders, Ganna, Andrea, Loboda, Andrey, Podgornaia, Anna, Lehtonen, Anne, Pitkäranta, Anne, Remes, Anne, Auranen, Annika, Hakanen, Antti, Palomäki, Antti, Jalanko, Anu, Loukola, Anu, Chhibber, Aparna, Lertratanakul, Apinya, Lehisto, Arto, Mannermaa, Arto, Hedman, Åsa, Chu, Audrey, Madar, Aviv, Ghazal, Awaisa, Challis, Benjamin, Sun, Benjamin, Cummings, Beryl, Riley-Gillis, Bridget, Fox, Caroline, Chen, Chia-Yen, Wang, Clarence, Chatelain, Clement, Gordin, Daniel, Quarless, Danjuma, Oh, Danny, Choy, David, Close, David, Pulford, David, Rice, David, Waterworth, Dawn, Rajpal, Deepak, Baird, Denis, Jambulingam, Dhanaprakash, Chang, Diana, Kulkarni, Diptee, Paul, Dirk, Liu, Dongyu, Teng, Edmond, Punkka, Eero, Ekholm, Eeva, Kangasniemi, Eeva, Laakkonen, Eija, Wigmore, Eleonor, Järvensivu, Elina, Kilpeläinen, Elina, Widen, Elisabeth, Tsai, Ellen, Mohammed, Elmutaz, Strauss, Erich, Kvikstad, Erika, Pitkänen, Esa, Kaiharju, Essi, Xu, Ethan, Xu, Fanli, Rahimov, Fedik, Vaura, Felix, Auge, Franck, Brein, Georg, Lassi, Glenda, Heap, Graham, Laivuori, Hannele, Mattsson, Hannele, Uusitalo-Järvinen, Hannele, Kankaanranta, Hannu, Uusitalo, Hannu, Chen, Hao, Siirtola, Harri, Joensuu, Heikki, Runz, Heiko, Lehtonen, Heli, Heyne, Henrike, Soininen, Hilkka, Jacob, Howard, Chen, Hubert, Shen, Huei-Yi, Xu, Huilei, Vähätalo, Iida, Kalliala, Ilkka, Tachmazidou, Ioanna, Kaprio, Jaakko, Parkkinen, Jaakko, Jacob, Jaison, Kumar, Janet, van Adelsberg, Janet, Laukkanen, Jari, Ritari, Jarmo, Garcia-Tabuenca, Javier, Waring, Jeffrey, Schutzman, Jennifer, Liu, Jimmy, Lee, Jiwoo, Betts, Joanna, Rämö, Joel, Huhtakangas, Johanna, Mäkelä, Johanna, Mattson, Johanna, Schleutker, Johanna, Kettunen, Johannes, Eicher, John, Zierer, Jonas, Chung, Jonathan, Turunen, Joni A., Gordillo, Jorge Esparza, Maranville, Joseph, Karjalainen, Juha, Mehtonen, Juha, Rinne, Juha, Sinisalo, Juha, Junttila, Juhani, Koskela, Jukka, Partanen, Jukka, Peltola, Jukka, Hunkapiller, Julie, Pihlajamäki, Jussi, Wade, Justin, Partanen, Juulia, Mäkikallio, Kaarin, Kaarniranta, Kai, Tasanen, Kaisa, Metsärinne, Kaj, Pärn, Kalle, King, Karen S., Eklund, Kari, Linden, Kari, Nieminen, Kari, Hannula-Jouppi, Katariina, Call, Katherine, Klinger, Katherine, Donner, Kati, Hyvärinen, Kati, Kristiansson, Kati, Kivinen, Katja, Kaukinen, Katri, Pylkäs, Katri, de Lange, Katrina, Usiskin, Keith, Palin, Kimmo, Shkura, Kirill, Auro, Kirsi, Kalpala, Kirsi, Sipilä, Kirsi, Elenius, Klaus, Tsuo, Kristin, Lahtela, L. Elisa, Addis, Laura, Huilaja, Laura, Kotaniemi-Talonen, Laura, Mustaniemi, Laura, Pirilä, Laura, Morin-Papunen, Laure, Aaltonen, Lauri, Koulu, Leena, Suominen, Liisa, Kallio, Lila, McCarthy, Linda, Aoxing, Liu, Männikkö, Lotta, Obeidat, Maen, Rivas, Manuel, Hautalahti, Marco, Pelkonen, Margit, Kaunisto, Mari, Niemi, Mari E., Siponen, Maria, Crohns, Marika, Kalaoja, Marita, Luodonpää, Marja, Vääräsmäki, Marja, Taskinen, Marja-Riitta, Tuppurainen, Marjo, Daly, Mark J., McCarthy, Mark, Laakso, Markku, Laukkanen, Markku, Voutilainen, Markku, Juonala, Markus, Perola, Markus, Hochfeld, Marla, Färkkilä, Martti, Reeve, Mary Pat, Kanai, Masahiro, Brauer, Matt, Gossel, Matthias, Peura, Matti, Ehm, Meg, Miller, Melissa, Liu, Mengzhen, Aavikko, Mervi, Koskinen, Miika, Helminen, Mika, Kähönen, Mika, Arvas, Mikko, Hiltunen, Mikko, Kiviniemi, Mikko, Caliskan, Minal, Karjalainen, Minna, Raivio, Minna, Koivusalo, Mirkka, Kurki, Mitja, Maasha, Mutaamba, Bing, Nan, Bowers, Natalie, Raghavan, Neha, Renaud, Nicole, Välimäki, Niko, Hautala, Nina, Mars, Nina, Pitkänen, Nina, Smaoui, Nizar, Kaipiainen-Seppänen, Oili, Carpén, Olli, Dada, Oluwaseun A., Soylemez, Onuralp, Heikinheimo, Oskari, Tuovila, Outi, Uimari, Outi, Gormley, Padhraig, Auvinen, Päivi, Laiho, Päivi, Mäntylä, Päivi, Polo, Päivi, Bronson, Paola, Kauppi, Paula, Karihtala, Peeter, Nieminen, Pekka, Tienari, Pentti, Virolainen, Petri, Isomäki, Pia, Della Briotta Parolo, Pietro, Pussinen, Pirkko, Palta, Priit, Pakkanen, Raimo, Serpi, Raisa, Mishra, Rajashree, Hinttala, Reetta, Kälviäinen, Reetta, Wong, Regis, Popovic, Relja, Siegel, Richard, Lahesmaa, Riitta, Kajanne, Risto, Graham, Robert, Plenge, Robert, Yang, Robert, Kallionpää, Roosa, Tian, Ruoyu, Miller, Russell, Esmaeeli, Sahar, Kauppila, Saila, John, Sally, Heikkinen, Sami, Koskelainen, Sami, Wadhawan, Samir, Pikkarainen, Sampsa, Heron, Samuel, Ripatti, Samuli, Seitsonen, Sanna, Lahdenperä, Sanni, Ruotsalainen, Sanni, Pendergrass, Sarah, Smith, Sarah, Vuoti, Sauli, Hassan, Shabbeer, Biswas, Shameek, Luo, Shuang, Rüeger, Sina, Lähteenmäki, Sini, Peltonen, Sirkku, Soini, Sirpa, Petrovski, Slavé, Ghosh, Soumitra, McDonough, Stefan, Loomis, Stephanie, Greenberg, Steven, Eaton, Susan, Lemmelä, Susanna, Xia, Tai-He, Laitinen, Tarja, Tukiainen, Taru, Salmi, Teea, Niiranen, Teemu, Paajanen, Teemu, Kuopio, Teijo, Kilpi, Terhi, Ollila, Terhi, Hiekkalinna, Tero, Jyrhämä, Tero, Harju, Terttu, Luukkaala, Tiina, Tuomi, Tiinamaija, Behrens, Tim, Lu, Tim, Blomster, Timo, Sipilä, Timo P., Southerington, Tom, Mäkelä, Tomi, Kiiskinen, Tuomo, Mantere, Tuomo, Meretoja, Tuomo, Bhangale, Tushar, Salo, Tuula, Sistonen, Tuuli, Palotie, Ulla, Gursoy, Ulvi, Kujala, Urho, Julkunen, Valtteri, Salomaa, Veikko, Kosma, Veli-Matti, Rathinakannan, Venkat Subramaniam, Kurra, Venla, Aaltonen, Vesa, Neduva, Victor, Llorens, Vincent, Sinha, Vishal, Anttonen, Vuokko, Zhou, Wei, Fleuren, Wilco, Chen, Xing, Hu, Xinli, Wu, Ying, Huang, Yunfeng, Terao, Chikashi, Zhao, Hongyu, Ebert, Benjamin L., Reilly, Muredach P., Ganna, Andrea, Machiela, Mitchell J., Genovese, Giulio, Natarajan, Pradeep·2021·Nature Medicine
DOI 10.1038/s41591-021-01371-0
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Abstract

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15–1.36; P = 1.8 × 10−7), including sepsis (HR 2.68; 95% CI = 2.25–3.19; P = 3.1 × 10−28), pneumonia (HR 1.76; 95% CI = 1.53–2.03; P = 2.3 × 10−15), digestive system infections (HR 1.51; 95% CI = 1.32–1.73; P = 2.2 × 10−9) and genitourinary infections (HR 1.25; 95% CI = 1.11–1.41; P = 3.7 × 10−4). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections. The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

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Authors
Zekavat, S. M., Lin, S.-H., Bick, A. G., Liu, A., Paruchuri, K., Wang, C., Uddin, M. M., Ye, Y., Yu, Z., Liu, X., Kamatani, Y., Bhattacharya, R., Pirruccello, J. P., Pampana, A., Loh, P.-R., Kohli, P., McCarroll, S. A., Kiryluk, K., Neale, B., Ionita-Laza, I., Engels, E. A., Brown, D. W., Smoller, J. W., Green, R., Karlson, E. W., Lebo, M., Ellinor, P. T., Weiss, S. T., Daly, M. J., The Biobank Japan Project, Koyama, S., Ito, K., Momozawa, Y., Matsuda, K., Yamanashi, Y., Furukawa, Y., Morisaki, T., Murakami, Y., Muto, K., Nagai, A., Obara, W., Yamaji, K., Takahashi, K., Asai, S., Takahashi, Y., Suzuki, T., Sinozaki, N., Yamaguchi, H., Minami, S., Murayama, S., Yoshimori, K., Nagayama, S., Obata, D., Higashiyama, M., Masumoto, A., Koretsune, Y., FinnGen Consortium, Palotie, A., Ziemann, A., Mitchell, A., Huertas-Vazquez, A., Salminen, A., Jussila, A., Havulinna, A., Mackay, A., Abbasi, A., Elliott, A., Cole, A., Shcherban, A., Mälarstig, A., Ganna, A., Loboda, A., Podgornaia, A., Lehtonen, A., Pitkäranta, A., Remes, A., Auranen, A., Hakanen, A., Palomäki, A., Jalanko, A., Loukola, A., Chhibber, A., Lertratanakul, A., Lehisto, A., Mannermaa, A., Hedman, Å., Chu, A., Madar, A., Ghazal, A., Challis, B., Sun, B., Cummings, B., Riley-Gillis, B., Fox, C., Chen, C.-Y., Wang, C., Chatelain, C., Gordin, D., Quarless, D., Oh, D., Choy, D., Close, D., Pulford, D., Rice, D., Waterworth, D., Rajpal, D., Baird, D., Jambulingam, D., Chang, D., Kulkarni, D., Paul, D., Liu, D., Teng, E., Punkka, E., Ekholm, E., Kangasniemi, E., Laakkonen, E., Wigmore, E., Järvensivu, E., Kilpeläinen, E., Widen, E., Tsai, E., Mohammed, E., Strauss, E., Kvikstad, E., Pitkänen, E., Kaiharju, E., Xu, E., Xu, F., Rahimov, F., Vaura, F., Auge, F., Brein, G., Lassi, G., Heap, G., Laivuori, H., Mattsson, H., Uusitalo-Järvinen, H., Kankaanranta, H., Uusitalo, H., Chen, H., Siirtola, H., Joensuu, H., Runz, H., Lehtonen, H., Heyne, H., Soininen, H., Jacob, H., Chen, H., Shen, H.-Y., Xu, H., Vähätalo, I., Kalliala, I., Tachmazidou, I., Kaprio, J., Parkkinen, J., Jacob, J., Kumar, J., van Adelsberg, J., Laukkanen, J., Ritari, J., Garcia-Tabuenca, J., Waring, J., Schutzman, J., Liu, J., Lee, J., Betts, J., Rämö, J., Huhtakangas, J., Mäkelä, J., Mattson, J., Schleutker, J., Kettunen, J., Eicher, J., Zierer, J., Chung, J., Turunen, J. A., Gordillo, J. E., Maranville, J., Karjalainen, J., Mehtonen, J., Rinne, J., Sinisalo, J., Junttila, J., Koskela, J., Partanen, J., Peltola, J., Hunkapiller, J., Pihlajamäki, J., Wade, J., Partanen, J., Mäkikallio, K., Kaarniranta, K., Tasanen, K., Metsärinne, K., Pärn, K., King, K. S., Eklund, K., Linden, K., Nieminen, K., Hannula-Jouppi, K., Call, K., Klinger, K., Donner, K., Hyvärinen, K., Kristiansson, K., Kivinen, K., Kaukinen, K., Pylkäs, K., de Lange, K., Usiskin, K., Palin, K., Shkura, K., Auro, K., Kalpala, K., Sipilä, K., Elenius, K., Tsuo, K., Lahtela, L. E., Addis, L., Huilaja, L., Kotaniemi-Talonen, L., Mustaniemi, L., Pirilä, L., Morin-Papunen, L., Aaltonen, L., Koulu, L., Suominen, L., Kallio, L., McCarthy, L., Aoxing, L., Männikkö, L., Obeidat, M., Rivas, M., Hautalahti, M., Pelkonen, M., Kaunisto, M., Niemi, M. E., Siponen, M., Crohns, M., Kalaoja, M., Luodonpää, M., Vääräsmäki, M., Taskinen, M.-R., Tuppurainen, M., Daly, M. J., McCarthy, M., Laakso, M., Laukkanen, M., Voutilainen, M., Juonala, M., Perola, M., Hochfeld, M., Färkkilä, M., Reeve, M. P., Kanai, M., Brauer, M., Gossel, M., Peura, M., Ehm, M., Miller, M., Liu, M., Aavikko, M., Koskinen, M., Helminen, M., Kähönen, M., Arvas, M., Hiltunen, M., Kiviniemi, M., Caliskan, M., Karjalainen, M., Raivio, M., Koivusalo, M., Kurki, M., Maasha, M., Bing, N., Bowers, N., Raghavan, N., Renaud, N., Välimäki, N., Hautala, N., Mars, N., Pitkänen, N., Smaoui, N., Kaipiainen-Seppänen, O., Carpén, O., Dada, O. A., Soylemez, O., Heikinheimo, O., Tuovila, O., Uimari, O., Gormley, P., Auvinen, P., Laiho, P., Mäntylä, P., Polo, P., Bronson, P., Kauppi, P., Karihtala, P., Nieminen, P., Tienari, P., Virolainen, P., Isomäki, P., Della Briotta Parolo, P., Pussinen, P., Palta, P., Pakkanen, R., Serpi, R., Mishra, R., Hinttala, R., Kälviäinen, R., Wong, R., Popovic, R., Siegel, R., Lahesmaa, R., Kajanne, R., Graham, R., Plenge, R., Yang, R., Kallionpää, R., Tian, R., Miller, R., Esmaeeli, S., Kauppila, S., John, S., Heikkinen, S., Koskelainen, S., Wadhawan, S., Pikkarainen, S., Heron, S., Ripatti, S., Seitsonen, S., Lahdenperä, S., Ruotsalainen, S., Pendergrass, S., Smith, S., Vuoti, S., Hassan, S., Biswas, S., Luo, S., Rüeger, S., Lähteenmäki, S., Peltonen, S., Soini, S., Petrovski, S., Ghosh, S., McDonough, S., Loomis, S., Greenberg, S., Eaton, S., Lemmelä, S., Xia, T.-H., Laitinen, T., Tukiainen, T., Salmi, T., Niiranen, T., Paajanen, T., Kuopio, T., Kilpi, T., Ollila, T., Hiekkalinna, T., Jyrhämä, T., Harju, T., Luukkaala, T., Tuomi, T., Behrens, T., Lu, T., Blomster, T., Sipilä, T. P., Southerington, T., Mäkelä, T., Kiiskinen, T., Mantere, T., Meretoja, T., Bhangale, T., Salo, T., Sistonen, T., Palotie, U., Gursoy, U., Kujala, U., Julkunen, V., Salomaa, V., Kosma, V.-M., Rathinakannan, V. S., Kurra, V., Aaltonen, V., Neduva, V., Llorens, V., Sinha, V., Anttonen, V., Zhou, W., Fleuren, W., Chen, X., Hu, X., Wu, Y., Huang, Y., Terao, C., Zhao, H., Ebert, B. L., Reilly, M. P., Ganna, A., Machiela, M. J., Genovese, G., & Natarajan, P.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-06
Volume
27
Issue
6
Pages
1012-1024
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-021-01371-0
OpenAlex
W3170166010
Cited by
198
References
14
FWCI
20.12
Type
journal article
Language
en
Open access
bronze

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Zekavat, S. M., Lin, S.-H., Bick, A. G., Liu, A., Paruchuri, K., Wang, C., Uddin, M. M., Ye, Y., Yu, Z., Liu, X., Kamatani, Y., Bhattacharya, R., Pirruccello, J. P., Pampana, A., Loh, P.-R., Kohli, P., McCarroll, S. A., Kiryluk, K., Neale, B., . . . Natarajan, P. (2021). Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. Nature Medicine. https://doi.org/10.1038/s41591-021-01371-0

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