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2. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

Author

Duperron, Marie-Gabrielle, Knol, Maria J., Le Grand, Quentin, Evans, Tavia E., Mishra, Aniket, Tsuchida, Ami, Roshchupkin, Gennady, Konuma, Takahiro, Trégouët, David-Alexandre, Romero, Jose Rafael, Frenzel, Stefan, Luciano, Michelle, Hofer, Edith, Bourgey, Mathieu, Dueker, Nicole D., Delgado, Pilar, Hilal, Saima, Tankard, Rick M., Dubost, Florian, Shin, Jean, Saba, Yasaman, Armstrong, Nicola J., Bordes, Constance, Bastin, Mark E., Beiser, Alexa, Brodaty, Henry, Bülow, Robin, Carrera, Caty, Chen, Christopher, Cheng, Ching-Yu, Deary, Ian J., Gampawar, Piyush G., Himali, Jayandra J., Jiang, Jiyang, Kawaguchi, Takahisa, Li, Shuo, Macalli, Melissa, Marquis, Pascale, Morris, Zoe, Muñoz Maniega, Susana, Miyamoto, Susumu, Okawa, Masakazu, Paradise, Matthew, Parva, Pedram, Rundek, Tatjana, Sargurupremraj, Muralidharan, Schilling, Sabrina, Setoh, Kazuya, Soukarieh, Omar, Tabara, Yasuharu, Teumer, Alexander, Thalamuthu, Anbupalam, Trollor, Julian N., Valdés Hernández, Maria C., Vernooij, Meike W., Völker, Uwe, Wittfeld, Katharina, Wong, Tien Yin, Wright, Margaret J., Zhang, Junyi, Zhao, Wanting, Zhu, Yi-Cheng, Schmidt, Helena, Sachdev, Perminder S., Wen, Wei, Yoshida, Kazumichi, Joutel, Anne, Satizabal, Claudia L., Sacco, Ralph L., Bourque, Guillaume, Lathrop, Mark, Paus, Tomas, Fernandez-Cadenas, Israel, Yang, Qiong, Mazoyer, Bernard, Boutinaud, Philippe, Okada, Yukinori, Grabe, Hans J., Mather, Karen A., Schmidt, Reinhold, Joliot, Marc, Ikram, M. Arfan, Matsuda, Fumihiko, Tzourio, Christophe, Wardlaw, Joanna M., Seshadri, Sudha, Adams, Hieab H. H., and Debette, Stéphanie

Published
2023
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3. Cerebral small vessel disease genomics and its implications across the lifespan.

Author

Sargurupremraj, Muralidharan, Suzuki, Hideaki, Jian, Xueqiu, Sarnowski, Chloé, Evans, Tavia E, Bis, Joshua C, Eiriksdottir, Gudny, Sakaue, Saori, Terzikhan, Natalie, Habes, Mohamad, Zhao, Wei, Armstrong, Nicola J, Hofer, Edith, Yanek, Lisa R, Hagenaars, Saskia P, Kumar, Rajan B, van den Akker, Erik B, McWhirter, Rebekah E, Trompet, Stella, Mishra, Aniket, Saba, Yasaman, Satizabal, Claudia L, Beaudet, Gregory, Petit, Laurent, Tsuchida, Ami, Zago, Laure, Schilling, Sabrina, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Amouyel, Philippe, Kwok, John B, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Kamatani, Yoichiro, Matsuda, Fumihiko, Psaty, Bruce M, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Trégouët, David-Alexandre, International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium (IHGC), Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, and Kardia, Sharon LR

Subjects
International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium, Humans, Alzheimer Disease, Hypertension, Medical History Taking, Risk Assessment, Risk Factors, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Genome-Wide Association Study, Young Adult, Diffusion Tensor Imaging, Genetic Loci, Mendelian Randomization Analysis, Cerebral Small Vessel Diseases, White Matter, and over
Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Published
2020

8. Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis

Author

Terao, Chikashi, Yoshifuji, Hajime, Matsumura, Takayoshi, Naruse, Taeko K., Ishii, Tomonori, Nakaoka, Yoshikazu, Kirino, Yohei, Matsuo, Keitaro, Origuchi, Tomoki, Shimizu, Masakazu, Maejima, Yasuhiro, Amiya, Eisuke, Tamura, Natsuko, Kawaguchi, Takahisa, Takahashi, Meiko, Setoh, Kazuya, Ohmura, Koichiro, Watanabe, Ryu, Horita, Tetsuya, Atsumi, Tatsuya, Matsukura, Mitsuru, Miyata, Tetsuro, Kochi, Yuta, Suda, Toshio, Tanemoto, Kazuo, Meguro, Akira, Okada, Yukinori, Ogimoto, Akiyoshi, Yamamoto, Motohisa, Takahashi, Hiroki, Nakayamada, Shingo, Saito, Kazuyoshi, Kuwana, Masataka, Mizuki, Nobuhisa, Tabara, Yasuharu, Ueda, Atsuhisa, Komuro, Issei, Kimura, Akinori, Isobe, Mitsuaki, Mimori, Tsuneyo, and Matsuda, Fumihiko

Published
2018

11. Transcriptomic Analysis Reveals Sixteen Potential Genes Associated with the Successful Differentiation of Antibody-Secreting Cells through the Utilization of Unfolded Protein Response Mechanisms in Robust Responders to the Influenza Vaccine.

Author

Tawfik, Ahmed, Kawaguchi, Takahisa, Takahashi, Meiko, Setoh, Kazuya, Yamaguchi, Izumi, Tabara, Yasuharu, Van Steen, Kristel, Sakuntabhai, Anavaj, and Matsuda, Fumihiko

Subjects
UNFOLDED protein response, INFLUENZA vaccines, HUMORAL immunity, CELL differentiation, VACCINE effectiveness, TRANSCRIPTOMES, HERPES zoster vaccines
Abstract

The seasonal influenza vaccine remains one of the vital recommended infection control measures for the elderly with chronic illnesses. We investigated the immunogenicity of a single dose of influenza vaccine in 123 seronegative participants and classified them into four distinct groups, determined by the promptness of vaccine response, the longevity of humoral immunity, and the likelihood of exhibiting cross-reactivity. Subsequently, we used transcriptional profiling and differential gene expression analysis to identify potential genes directly associated with the robust response to the vaccine. The group of exemplary vaccine responders differentially expressed 16 genes, namely: MZB1, MYDGF, TXNDC5, TXNDC11, HSP90B1, FKBP11, PDIA5, PRDX4, CD38, SDC1, TNFRSF17, TNFRSF13B, PAX5, POU2AF1, IRF4, and XBP1. Our findings point out a list of expressed proteins that are related to B cell proliferation, unfolded protein response, and cellular haemostasis, as well as a linkage of these expressions to the survival of long-lived plasma cells. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Associations between Sleep-Disordered Breathing and Serum Uric Acid and Their Sex Differences: The Nagahama Study

Author

Sunadome, Hironobu, primary, Murase, Kimihiko, additional, Tabara, Yasuharu, additional, Matsumoto, Takeshi, additional, Minami, Takuma, additional, Kanai, Osamu, additional, Nagasaki, Tadao, additional, Takahashi, Naomi, additional, Hamada, Satoshi, additional, Tanizawa, Kiminobu, additional, Togawa, Jumpei, additional, Uiji, Sayaka, additional, Wakamura, Tomoko, additional, Komenami, Naoko, additional, Setoh, Kazuya, additional, Kawaguchi, Takahisa, additional, Morita, Satoshi, additional, Takahashi, Yoshimitsu, additional, Nakayama, Takeo, additional, Hirai, Toyohiro, additional, Sato, Susumu, additional, Matsuda, Fumihiko, additional, and Chin, Kazuo, additional

Published
2023
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13. Genetic variants for head size share genes and pathways with cancer

Author

Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S., Bastin, Mark E., Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L., Deary, Ian J., Fleischman, Debra A., Gottesman, Rebecca F., Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J. Wouter, Liewald, David C.M., Lopez, Lorna M., Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J., Nyquist, Paul, Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M., Yanek, Lisa, Yang, Jingyun, Agartz, Ingrid, Alhusaini, Saud, Almasy, Laura, Ames, David, Amunts, Katrin, Andreassen, Ole A., Armstrong, Nicola, Bernard, Manon, Blangero, John, Blanken, Laura M.E., Boks, Marco P., Boomsma, Dorret I., Brickman, Adam M., Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Carr, Vaughan J., Catts, Stanley V., Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R.K., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Davies, Gareth E., de Geus, Eco J.C., de Zubicaray, Greig I., den Braber, Anouk, Desrivières, Sylvane, Dillman, Allissa, Djurovic, Srdjan, Drevets, Wayne C., Duggirala, Ravi, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana M., Ge, Tian, Giddaluru, Sudheer, Glahn, David C., Goldman, Aaron L., Green, Robert C., Greven, Corina U., Grimm, Oliver, Hansell, Narelle K., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans, Hibar, Derrek P., Ho, Beng-Choon, Hoekstra, Pieter J., Holmes, Avram J., Hoogman, Martine, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Jablensky, Assen, Jenkinson, Mark, Jia, Tianye, Jöckel, Karl-Heinz, Jönsson, Erik G., Kim, Sungeun, Klein, Marieke, Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Le Hellard, Stephanie, Lemaître, Hervé, Loughland, Carmel, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Matarin, Mar, Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., McDonald, Colm, McMahon, Francis J., McMahon, Katie L., E, Rebekah, McWhirter, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Michie, Patricia T., Milaneschi, Yuri, Morris, Derek W., Mowry, Bryan, Nho, Kwangsik, Nichols, Thomas E., Nöthen, Markus N., Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Pantelis, Christos, Pappa, Irene, Penninx, Brenda, Pike, G. Bruce, Rasser, Paul E., Rentería, Miguel E., Reppermund, Simone, Rietschel, Marcella, Risacher, Shannon L., Romanczuk-Seiferth, Nina, Rose, Emma Jane, Sachdev, Perminder S., Sämann, Philipp G., Saykin, Andrew J., Schall, Ulrich, Schofield, Peter R., Schramm, Sara, Schumann, Gunter, Scott, Rodney, Shen, Li, Sisodiya, Sanjay M., Soininen, Hilkka, Sprooten, Emma, Srikanth, Velandai, Steen, Vidar M., Strike, Lachlan T., Thalamuthu, Anbupalam, Toga, Arthur W., Tooney, Paul, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Valdés Hernández, Maria del C., van der Meer, Dennis, Van der Wee, Nic J.A., Van Haren, Neeltje E.M., van 't Ent, Dennis, Veltman, Dick J., Walter, Henrik, Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, Winkler, Anderson M., Woldehawariat, Girma, Wright, Margaret J., Wu, Jingqin, Knol, Maria J., Poot, Raymond A., Evans, Tavia E., Satizabal, Claudia L., Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C., van Dam-Nolen, Dianne H.K., Lamballais, Sander, Pawlak, Mikolaj A., Lewis, Cora E., Carrion-Castillo, Amaia, van Erp, Theo G.M., Reinbold, Céline S., Shin, Jean, Scholz, Markus, Håberg, Asta K., Kämpe, Anders, Li, Gloria H.Y., Avinun, Reut, Atkins, Joshua R., Hsu, Fang-Chi, Amod, Alyssa R., Lam, Max, Tsuchida, Ami, Teunissen, Mariël W.A., Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S., Beyer, Frauke, Bis, Joshua C., Bos, Daniel, Bryan, R. Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte A.M., Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M., Franke, Barbara, Freedman, Barry I., Friedrich, Nele, Green, Melissa J., Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M. Kamran, Jack, Clifford R., Jr., Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R., Li, Shuo, Lim, Keane, Longstreth, W.T., Macciardi, Fabio, Mäkitie, Outi, Mazoyer, Bernard, Medland, Sarah E., Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H., Muetzel, Ryan, Mühleisen, Thomas W., Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D., Pausova, Zdenka, Preda, Adrian, Quidé, Yann, Reay, William R., Roshchupkin, Gennady V., Schmidt, Reinhold, Schreiner, Pamela J., Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L., Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W., Werring, David J., Windham, B. Gwen, Witte, A. Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G., Le Grand, Quentin, Sim, Kang, Stein, Dan J., Bowden, Donald W., Cairns, Murray J., Hariri, Ahmad R., Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D., Crivello, Fabrice, Launer, Lenore J., White, Tonya, Koudstaal, Peter J., Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J., Ikram, M. Arfan, Debette, Stéphanie, Thompson, Paul M., Seshadri, Sudha, and Adams, Hieab H.H.

Published
2024
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15. Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism: A Multicenter Study in Japan

Author

Ohno, Youichi, Sone, Masakatsu, Inagaki, Nobuya, Yamasaki, Toshinari, Ogawa, Osamu, Takeda, Yoshiyu, Kurihara, Isao, Itoh, Hiroshi, Umakoshi, Hironobu, Tsuiki, Mika, Ichijo, Takamasa, Katabami, Takuyuki, Tanaka, Yasushi, Wada, Norio, Shibayama, Yui, Yoshimoto, Takanobu, Ogawa, Yoshihiro, Kawashima, Junji, Takahashi, Katsutoshi, Fujita, Megumi, Watanabe, Minemori, Matsuda, Yuichi, Kobayashi, Hiroki, Shibata, Hirotaka, Kamemura, Kohei, Otsuki, Michio, Fujii, Yuichi, Yamamoto, Koichi, Ogo, Atsushi, Okamura, Shintaro, Miyauchi, Shozo, Fukuoka, Tomikazu, Izawa, Shoichiro, Yoneda, Takashi, Hashimoto, Shigeatsu, Yanase, Toshihiko, Suzuki, Tomoko, Kawamura, Takashi, Tabara, Yasuharu, Matsuda, Fumihiko, Naruse, Mitsuhide, Kawaguchi, Takahisa, Setoh, Kazuya, Matsuda, Fumihiko, Takahashi, Yoshimitsu, Nakayama, Takeo, and Kosugi, Shinji

Published
2018
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18. Sleep disordered breathing and metabolic comorbidities across gender and menopausal status in East Asians; the Nagahama Study

Author

Matsumoto, Takeshi, Murase, Kimihiko, Tabara, Yasuharu, Minami, Takuma, Kanai, Osamu, Takeyama, Hirofumi, Takahashi, Naomi, Hamada, Satoshi, Tanizawa, Kiminobu, Wakamura, Tomoko, Komenami, Naoko, Setoh, Kazuya, Kawaguchi, Takahisa, Tsutsumi, Takanobu, Morita, Satoshi, Takahashi, Yoshimitsu, Nakayama, Takeo, Hirai, Toyohiro, Matsuda, Fumihiko, and Chin, Kazuo

Subjects
obesity, hypertension, diabetes, Sleep disordered breathing, sex difference, mental disorders, dyslipidemia, menopause, cardiovascular diseases, general population, metabolic syndrome, nervous system diseases, respiratory tract diseases
Abstract

It is well known that the prevalence of sleep disordered breathing (SDB) is increased in patients with obesity or metabolic comorbidities. However, the way in which the prevalence of SDB increases in relation to comorbidities according to the severity of obesity remains unclear. This cross-sectional study evaluated 7713 community participants with nocturnal oximetry ≥2 nights. SDB was assessed by the 3% oxygen desaturation index corrected for sleep duration obtained by wrist actigraphy (Acti-ODI3%). SDB severity was defined by Acti-ODI3%. Obesity was defined as body mass index ≥25 kg·/m−2. The prevalence of SDB was 41.0% (95% CI 39.9–42.1), 46.9% (45.8–48.0), 10.1% (9.5–10.8), and 2.0% (1.7–2.3) in normal, mild, moderate, and severe SDB, respectively, with notable sex differences evident (men >post-menopausal women >pre-menopausal women). Comorbidities such as hypertension, diabetes, and metabolic syndrome were independently associated with the prevalence of moderate-to-severe SDB, and coincidence of any one of these with obesity was associated with a higher probability of moderate-to-severe SDB (OR 8.2, 95% CI 6.6–10.2; 7.8, 5.6–10.9; 6.7, 5.2–8.6, respectively). Dyslipidemia in addition to obesity was not additively associated with the prevalence of moderate to-severe SDB. The number of antihypertensive drugs was associated with SDB (p for trend, 生活習慣病に睡眠時無呼吸症候群がひそむことを解明 --アジア最大資料数のながはまコホートより--. 京都大学プレスリリース. 2020-05-19.

Published
2020

20. Sleep disordered breathing and metabolic comorbidities across sex and menopausal status in East Asians: the Nagahama Study

Author

Matsumoto, Takeshi, primary, Murase, Kimihiko, additional, Tabara, Yasuharu, additional, Minami, Takuma, additional, Kanai, Osamu, additional, Takeyama, Hirofumi, additional, Takahashi, Naomi, additional, Hamada, Satoshi, additional, Tanizawa, Kiminobu, additional, Wakamura, Tomoko, additional, Komenami, Naoko, additional, Setoh, Kazuya, additional, Kawaguchi, Takahisa, additional, Tsutsumi, Takanobu, additional, Morita, Satoshi, additional, Takahashi, Yoshimitsu, additional, Nakayama, Takeo, additional, Hirai, Toyohiro, additional, Matsuda, Fumihiko, additional, and Chin, Kazuo, additional

Published
2020
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21. Association of ALPL variants with serum alkaline phosphatase and bone traits in the general Japanese population: The Nagahama Study

Author

Nagata, Miho, primary, Setoh, Kazuya, additional, Takahashi, Meiko, additional, Higasa, Koichiro, additional, Kawaguchi, Takahisa, additional, Kawasaki, Hidenori, additional, Wada, Takahito, additional, Watanabe, Atsushi, additional, Sawai, Hideaki, additional, Tabara, Yasuharu, additional, Yamada, Takahiro, additional, Matsuda, Fumihiko, additional, and Kosugi, Shinji, additional

Published
2019
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24. Brachial-ankle pulse wave velocity and cardio-ankle vascular index are associated with future cardiovascular events in a general population: The Nagahama Study.

Author

Yasuharu, Tabara, Setoh, Kazuya, Kawaguchi, Takahisa, Nakayama, Takeo, Matsuda, Fumihiko, and Nagahama study group

Abstract

Faster pulse wave velocity (PWV) is known to be associated with the incidence of cardiovascular diseases (CVD). The aim of this study was to clarify the hypothesis that PWV may be associated with future CVD events even when its time-dependent changes were adjusted. We also investigated a prognostic significance of cardio-ankle vascular index, another index of arterial stiffness. Study participants included 8850 community residents. The repeated measures of the clinical parameters at 5.0 years after the baseline were available for 7249 of the participants. PWV was calculated using the arterial waveforms measured at the brachia and ankles (baPWV). The cardio-ankle vascular index was calculated by estimated pulse transit time from aortic valve to tibial artery. During the 8.53 years follow-up period, we observed 215 cases of CVD. The incidence rate increased linearly with baPWV quartiles (per 10 000 person-years: Q1, 2.7; Q2, 12.6; Q3, 22.5; Q4, 76.2), and the highest quartile was identified as an independent determinant of incident CVD by conventional Cox proportional hazard analysis adjusted for known risk factors [hazard ratio (HR), 4.00; p = .007]. Per unit HR of baPWV (HR, 1.15; p < .001) remained significant in the time-dependent Cox regression analysis including baPWV and other clinical values measured at 5-year after the baseline as time-varying variables (HR, 1.14; p < .001). The cardio-ankle vascular index was also associated with CVD with similar manner though the associations were less clear than that of baPWV. baPWV is a good risk marker for the incidence of CVD. [ABSTRACT FROM AUTHOR]

Published
2021
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25. Genetic variants for head size share genes and pathways with cancer

Author

Knol, Maria J., Poot, Raymond A., Evans, Tavia E., Satizabal, Claudia L., Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C., van Dam-Nolen, Dianne H.K., Lamballais, Sander, Pawlak, Mikolaj A., Lewis, Cora E., Carrion-Castillo, Amaia, van Erp, Theo G.M., Reinbold, Céline S., Shin, Jean, Scholz, Markus, Håberg, Asta K., Kämpe, Anders, Li, Gloria H.Y., Avinun, Reut, Atkins, Joshua R., Hsu, Fang-Chi, Amod, Alyssa R., Lam, Max, Tsuchida, Ami, Teunissen, Mariël W.A., Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S., Beyer, Frauke, Bis, Joshua C., Bos, Daniel, Bryan, R. Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte A.M., Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M., Franke, Barbara, Freedman, Barry I., Friedrich, Nele, Green, Melissa J., Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M. Kamran, Jack, Clifford R., Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R., Li, Shuo, Lim, Keane, Longstreth, W.T., Macciardi, Fabio, Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S., Bastin, Mark E., Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L., Deary, Ian J., Fleischman, Debra A., Gottesman, Rebecca F., Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J. Wouter, Liewald, David C.M., Lopez, Lorna M., Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J., Nyquist, Paul, Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M., Yanek, Lisa, Yang, Jingyun, Agartz, Ingrid, Alhusaini, Saud, Almasy, Laura, Ames, David, Amunts, Katrin, Andreassen, Ole A., Armstrong, Nicola, Bernard, Manon, Blangero, John, Blanken, Laura M.E., Boks, Marco P., Boomsma, Dorret I., Brickman, Adam M., Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Carr, Vaughan J., Catts, Stanley V., Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R.K., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Davies, Gareth E., de Geus, Eco J.C., de Zubicaray, Greig I., den Braber, Anouk, Desrivières, Sylvane, Dillman, Allissa, Djurovic, Srdjan, Drevets, Wayne C., Duggirala, Ravi, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana M., Ge, Tian, Giddaluru, Sudheer, Glahn, David C., Goldman, Aaron L., Green, Robert C., Greven, Corina U., Grimm, Oliver, Hansell, Narelle K., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans, Hibar, Derrek P., Ho, Beng-Choon, Hoekstra, Pieter J., Holmes, Avram J., Hoogman, Martine, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Jablensky, Assen, Jenkinson, Mark, Jia, Tianye, Jöckel, Karl-Heinz, Jönsson, Erik G., Kim, Sungeun, Klein, Marieke, Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Le Hellard, Stephanie, Lemaître, Hervé, Loughland, Carmel, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Matarin, Mar, Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., McDonald, Colm, McMahon, Francis J., McMahon, Katie L., E, Rebekah, McWhirter, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Michie, Patricia T., Milaneschi, Yuri, Morris, Derek W., Mowry, Bryan, Nho, Kwangsik, Nichols, Thomas E., Nöthen, Markus N., Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Pantelis, Christos, Pappa, Irene, Penninx, Brenda, Pike, G. Bruce, Rasser, Paul E., Rentería, Miguel E., Reppermund, Simone, Rietschel, Marcella, Risacher, Shannon L., Romanczuk-Seiferth, Nina, Rose, Emma Jane, Sachdev, Perminder S., Sämann, Philipp G., Saykin, Andrew J., Schall, Ulrich, Schofield, Peter R., Schramm, Sara, Schumann, Gunter, Scott, Rodney, Shen, Li, Sisodiya, Sanjay M., Soininen, Hilkka, Sprooten, Emma, Srikanth, Velandai, Steen, Vidar M., Strike, Lachlan T., Thalamuthu, Anbupalam, Toga, Arthur W., Tooney, Paul, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Valdés Hernández, Maria del C., van der Meer, Dennis, Van der Wee, Nic J.A., Van Haren, Neeltje E.M., van 't Ent, Dennis, Veltman, Dick J., Walter, Henrik, Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, Winkler, Anderson M., Woldehawariat, Girma, Wright, Margaret J., Wu, Jingqin, Mäkitie, Outi, Mazoyer, Bernard, Medland, Sarah E., Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H., Muetzel, Ryan, Mühleisen, Thomas W., Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D., Pausova, Zdenka, Preda, Adrian, Quidé, Yann, Reay, William R., Roshchupkin, Gennady V., Schmidt, Reinhold, Schreiner, Pamela J., Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L., Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W., Werring, David J., Windham, B. Gwen, Witte, A. Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G., Le Grand, Quentin, Sim, Kang, Stein, Dan J., Bowden, Donald W., Cairns, Murray J., Hariri, Ahmad R., Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D., Crivello, Fabrice, Launer, Lenore J., White, Tonya, Koudstaal, Peter J., Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J., Ikram, M. Arfan, Debette, Stéphanie, Thompson, Paul M., Seshadri, Sudha, and Adams, Hieab H.H.

Abstract

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Published
2024
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26. Prevalence of posterior staphyloma and factors associated with its shape in the Japanese population

Author

Numa, Shogo, Yamashiro, Kenji, Wakazono, Tomotaka, Yoshikawa, Munemitsu, Miyake, Masahiro, Nakanishi, Hideo, Oishi, Akio, Kawaguchi, Takahisa, Setoh, Kazuya, Takahashi, Yoshimitsu, Kosugi, Shinji, Nakayama, Takeo, Tabara, Yasuharu, Matsuda, Fumihiko, Yoshimura, Nagahisa, and Tsujikawa, Akitaka

Subjects
genetic structures, sense organs, eye diseases
Abstract

Myopia is increasing rapidly worldwide. We performed a cross-sectional study to investigate the prevalence of posterior staphyloma, a complication of myopia, and its shape characteristics in relation to age, sex, and axial length (AL) in a Japanese community-based cohort. The right eyes of 3748 participants who underwent fundus photography and optical coherence tomography (OCT) examination were evaluated. Posterior staphyloma prevalence was evaluated using fundus photographs and OCT images. Furthermore, fundus shapes were analyzed by measuring local fundus curvatures on 6 mm cross-line OCT images at intervals of 1 µm. The mean and variance of the curvatures were calculated to represent the fundus shape of each eye for investigation of the relationship between fundus curvature and age, sex, and AL. Seventy-seven eyes (2.05%) had posterior staphyloma. The mean and variance of the fundus curvatures were significantly greater in women than in men and became greater with age, suggesting that the shape of the staphyloma was steeper and less smooth in women and elderly subjects. AL and mean curvature showed a significant correlation (P = 2 × 10⁻¹⁶, R = 0.480), which was significantly affected by age (P

Published
2018

27. Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson.

Author

Hosoda, Yoshikatsu, Miyake, Masahiro, Meguro, Akira, Tabara, Yasuharu, Iwai, Sachiko, Ueda-Arakawa, Naoko, Nakano, Eri, Mori, Yuki, Yoshikawa, Munemitsu, Nakanishi, Hideo, Khor, Chiea-Chuen, Saw, Seang-Mei, Yamada, Ryo, Matsuda, Fumihiko, Cheng, Ching-Yu, Mizuki, Nobuhisa, Tsujikawa, Akitaka, Yamashiro, Kenji, Kawaguchi, Takahisa, and Setoh, Kazuya

Subjects
KERATOCONUS, ARTIFICIAL intelligence, GENOMES, COMPUTER systems, CORNEAL transplantation
Abstract

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10−13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development. Yoshikatsu Hosoda et al. study the genetic basis for central corneal thickness (CCT) that is associated with keratoconus. They identify two susceptibility loci, STON2 rs2371597 and SMAD3 rs12913547, using two-step genome-wide association study (GWAS) and predictive analysis with IBM's Watson question answering computer system, respectively. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Relationship among Chlamydia and Mycoplasma Pneumoniae Seropositivity, IKZF1 Genotype and Chronic Obstructive Pulmonary Disease in A General Japanese Population

Author

Muro, Shigeo, Tabara, Yasuharu, Matsumoto, Hisako, Setoh, Kazuya, Kawaguchi, Takahisa, Takahashi, Meiko, Ito, Isao, Ito, Yutaka, Murase, Kimihiko, Terao, Chikashi, Kosugi, Shinji, Yamada, Ryo, Sekine, Akihiro, Nakayama, Takeo, Chin, Kazuo, Mishima, Michiaki, and Matsuda, Fumihiko

Subjects
respiratory tract diseases
Abstract

Chronic obstructive pulmonary disease (COPD) is a possible risk factor for cardiovascular disease. The association of COPD with the pathogenicity of infection with Chlamydia pneumoniae and Mycoplasma pneumoniae is controversial. We conducted a cross-sectional study to clarify the association between atypical pneumoniae seropositivity and COPD in a general population. We also investigated genetic polymorphisms conferring susceptibility to a pneumonia titer. The study included 9040 Japanese subjects (54±13 years). COPD was defined as a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 70%. Serum levels of IgA and IgG antibodies to C pneumoniae were determined using an enzyme-linked immunoassay, and M pneumoniae seropositivity was assessed by a particle agglutination test. Subjects seropositive for C pneumoniae (26.1%) had a higher prevalence of COPD (seropositive, 5.8%; seronegative, 3.1%; P

Published
2016

30. A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

Author

Ohigashi, Izumi, primary, Ohte, Yuki, additional, Setoh, Kazuya, additional, Nakase, Hiroshi, additional, Maekawa, Akiko, additional, Kiyonari, Hiroshi, additional, Hamazaki, Yoko, additional, Sekai, Miho, additional, Sudo, Tetsuo, additional, Tabara, Yasuharu, additional, Sawai, Hiromi, additional, Omae, Yosuke, additional, Yuliwulandari, Rika, additional, Tanaka, Yasuhito, additional, Mizokami, Masashi, additional, Inoue, Hiroshi, additional, Kasahara, Masanori, additional, Minato, Nagahiro, additional, Tokunaga, Katsushi, additional, Tanaka, Keiji, additional, Matsuda, Fumihiko, additional, Murata, Shigeo, additional, and Takahama, Yousuke, additional

Published
2017
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31. Combined association of clinical and lifestyle factors with non-restorative sleep: The Nagahama Study

Author

Matsumoto, Takeshi, primary, Tabara, Yasuharu, additional, Murase, Kimihiko, additional, Takahashi, Yoshimitsu, additional, Setoh, Kazuya, additional, Kawaguchi, Takahisa, additional, Muro, Shigeo, additional, Kadotani, Hiroshi, additional, Kosugi, Shinji, additional, Sekine, Akihiro, additional, Yamada, Ryo, additional, Nakayama, Takeo, additional, Mishima, Michiaki, additional, Matsuda, Fumihiko, additional, and Chin, Kazuo, additional

Published
2017
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32. Association of ALPLvariants with serum alkaline phosphatase and bone traits in the general Japanese population: The Nagahama Study

Author

Nagata, Miho, Setoh, Kazuya, Takahashi, Meiko, Higasa, Koichiro, Kawaguchi, Takahisa, Kawasaki, Hidenori, Wada, Takahito, Watanabe, Atsushi, Sawai, Hideaki, Tabara, Yasuharu, Yamada, Takahiro, Matsuda, Fumihiko, and Kosugi, Shinji

Abstract

Although alkaline phosphatase (ALP) activity is relatively low in carriers of recessive type hypophosphatasia (HPP), most are asymptomatic and therefore do not undergo medical evaluations. We analyzed the association of ALP-encoding ALPLvariants with serum ALP and bone traits in the general Japanese population. Study participants (n= 9671) were from the Nagahama Study, which was a longitudinal cohort study of an apparently healthy general Japanese population. ALPLvariants were analyzed by whole-genome sequencing or TaqMan probe assays using DNA extracted from peripheral blood samples. The speed of sound in calcaneal bone was assessed by quantitative ultrasound (QUS) and used as surrogate measures of bone mineral density. We identified 13 ALPLvariants. Minor allele frequencies of three variants were higher than expected. Variant c.529G > A has been reported as a possible pathogenic variant for adult type HPP. Variants c.979C > T and c.1559delT are reported as pathogenic variants for perinatal severe HPP or infantile HPP. The allele frequencies of c.529G > A, c.979C > T, and c.1559delT were 0.0107, 0.0040, and 0.0014, respectively. Serum ALP activity was significantly lower and differed among the three variants (P< 0.001), as well as between individuals with and without any of the three variants (P< 0.001). Serum ALP activity was inversely associated with QUS values, although no direct association was observed between the ALPLvariants and QUS values. An association between serum ALP activity and QUS was confirmed; however, we failed to detect an association between ALPLvariants and bone traits in the general Japanese population.

Published
2020
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33. Knee Pain and Low Back Pain Additively Disturb Sleep in the General Population: A Cross-Sectional Analysis of the Nagahama Study

Author

Murase, Kimihiko, primary, Tabara, Yasuharu, additional, Ito, Hiromu, additional, Kobayashi, Masahiko, additional, Takahashi, Yoshimitsu, additional, Setoh, Kazuya, additional, Kawaguchi, Takahisa, additional, Muro, Shigeo, additional, Kadotani, Hiroshi, additional, Kosugi, Shinji, additional, Sekine, Akihiro, additional, Yamada, Ryo, additional, Nakayama, Takeo, additional, Mishima, Michiaki, additional, Matsuda, Shuichi, additional, Matsuda, Fumihiko, additional, and Chin, Kazuo, additional

Published
2015
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34. Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels

Author

Setoh, Kazuya, primary, Terao, Chikashi, additional, Muro, Shigeo, additional, Kawaguchi, Takahisa, additional, Tabara, Yasuharu, additional, Takahashi, Meiko, additional, Nakayama, Takeo, additional, Kosugi, Shinji, additional, Sekine, Akihiro, additional, Yamada, Ryo, additional, Mishima, Michiaki, additional, and Matsuda, Fumihiko, additional

Published
2015
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37. Relationship Among Chlamydia and Mycoplasma Pneumoniae Seropositivity, IKZF1Genotype and Chronic Obstructive Pulmonary Disease in A General Japanese Population

Author

Muro, Shigeo, Tabara, Yasuharu, Matsumoto, Hisako, Setoh, Kazuya, Kawaguchi, Takahisa, Takahashi, Meiko, Ito, Isao, Ito, Yutaka, Murase, Kimihiko, Terao, Chikashi, Kosugi, Shinji, Yamada, Ryo, Sekine, Akihiro, Nakayama, Takeo, Chin, Kazuo, Mishima, Michiaki, Matsuda, Fumihiko, and Zhou., Xu-jie

Abstract

Supplemental Digital Content is available in the text

Published
2016
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38. Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.

Author

Koyanagi YN, Nakatochi M, Namba S, Oze I, Charvat H, Narita A, Kawaguchi T, Ikezaki H, Hishida A, Hara M, Takezaki T, Koyama T, Nakamura Y, Suzuki S, Katsuura-Kamano S, Kuriki K, Nakamura Y, Takeuchi K, Hozawa A, Kinoshita K, Sutoh Y, Tanno K, Shimizu A, Ito H, Kasugai Y, Kawakatsu Y, Taniyama Y, Tajika M, Shimizu Y, Suzuki E, Hosono Y, Imoto I, Tabara Y, Takahashi M, Setoh K, Matsuda K, Nakano S, Goto A, Katagiri R, Yamaji T, Sawada N, Tsugane S, Wakai K, Yamamoto M, Sasaki M, Matsuda F, Okada Y, Iwasaki M, Brennan P, and Matsuo K

Subjects
Humans, Polymorphism, Single Nucleotide, Alcohol Drinking genetics, Genotype, Aldehyde Dehydrogenase, Mitochondrial genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Esophageal Neoplasms epidemiology, Esophageal Neoplasms genetics, East Asian People
Abstract

An East Asian-specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four ( GCKR , ADH1B , ALDH1A1 , and ALDH2 ) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

Published
2024
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39. Associations Among Tooth Loss, Periodontitis, and Carotid Intima-Media Thickness: the Nagahama Study.

Author

Fukuhara S, Watanabe T, Yamazaki T, Yamanaka S, Nakao K, Asai K, Kashiwagi M, Yamazaki A, Umebachi C, Setoh K, Tabara Y, Nakayama T, Matsuda F, and Bessho K

Subjects
Humans, Carotid Intima-Media Thickness, Cross-Sectional Studies, Risk Factors, Inflammation complications, Tooth Loss epidemiology, Tooth Loss complications, Carotid Artery Diseases complications, Periodontitis complications, Periodontitis epidemiology, Atherosclerosis epidemiology, Atherosclerosis complications
Abstract

Aims: This study aimed to clarify the relationships among tooth loss, periodontal condition, and subclinical atherosclerosis from the aspect of intensity, extent, and duration of inflammation., Methods: This cross-sectional study included 9,778 people from the Nagahama Study, a large-scale, general population-based study conducted in Japan. The number of teeth and periodontal status, including the attachment level (AL) and pocket depth (PD) of representative teeth from six regions, were evaluated by dentists. The maximum intima-media thickness (IMT) of the common carotid artery was used as an index of atherosclerosis., Results: In the multivariate analysis adjusted for conventional risk factors, a large number of missing teeth (＜9 remaining teeth), which related to long-lasting inflammation indicative of the highest stage of periodontitis, was identified as an independent determinant of IMT in a general population (coefficient: 0.042; 95% confidence interval [CI]: 0.016 to 0.068). The presence of two or more regions with an AL ≥4 mm, which is indicative of the progressing, long-lasting stages of periodontal inflammation, was also independently associated with IMT (coefficient: 0.016; 95% CI: 0.004 to 0.028). On the contrary, PD, a measure of the early and reversible phases of periodontal inflammation, and loss of AL in the group without tooth loss were not significantly associated with IMT, because of the limited degree of accumulated periodontitis., Conclusion: The present results suggest that the association between periodontitis and atherosclerosis depends on the inflammation intensity, extent, and duration.

Published
2023
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40. Differences between subjective and objective sleep duration according to actual sleep duration and sleep-disordered breathing: the Nagahama Study.

Author

Takahashi N, Matsumoto T, Nakatsuka Y, Murase K, Tabara Y, Takeyama H, Minami T, Hamada S, Kanai O, Tanizawa K, Nakamoto I, Kawaguchi T, Setoh K, Tsutsumi T, Takahashi Y, Handa T, Wakamura T, Komenami N, Morita S, Hirai T, Matsuda F, Nakayama T, and Chin K

Subjects
Actigraphy, Cross-Sectional Studies, Female, Humans, Male, Oxygen, Sleep, Sleep Apnea Syndromes complications, Sleep Apnea Syndromes epidemiology
Abstract

Study Objectives: Since subjective sleep duration (SSD) is considered to be longer than objective sleep duration (OSD), results of SSD minus OSD (SSD-OSD) might always be thought to be positive. Some recent reports showed different results, but exact results have not been obtained. The difference between SSD and OSD may change according to OSD. We investigated this difference and its association with sleep-disordered breathing (SDB) or nonrestorative sleep., Methods: This cross-sectional study evaluated 6,908 community residents in Nagahama, Japan. SSD was determined by self-administered questionnaire. OSD was measured by wrist actigraphy and sleep diary. SDB was assessed according to the 3% oxygen desaturation index adjusted for OSD., Results: Worthy of notice was that SSD was shorter than OSD for those with SSD longer than 6.98 hours in all participants, 7.36 hours in males, and 6.80 hours in females. However, SSD was longer than OSD (mean ± SD: 6.49 ± 1.07 vs 6.01 ± 0.96; P < .001) overall, as SSD is considered to be longer than OSD. In patients with SDB, the difference between SSD-OSD was greater when OSD was s horter. The difference also depended on SDB severity. The degree of positivity between OSD and SSD was a significant factor in nonrestorative sleep (odds ratio: 2.691; P < .001)., Conclusions: When OSD was slightly less than 7 (6.98) hours, participants reported or perceived SSD > OSD. When OSD was > 6.98 hours, participants reported or perceived SSD < OSD. Patients with SDB reported longer SSD than OSD according to severity of SDB. Evaluating SSD, OSD, and their differences may be useful for managing sleep disturbances, including nonrestorative sleep., Citation: Takahashi N, Matsumoto T, Nakatsuka Y, et al. Differences between subjective and objective sleep duration according to actual sleep duration and sleep-disordered breathing: the Nagahama Study. J Clin Sleep Med . 2022;18(3):851-859., (© 2022 American Academy of Sleep Medicine.)

Published
2022
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41. Impact of sleep-disordered breathing on glucose metabolism among individuals with a family history of diabetes: the Nagahama study.

Author

Minami T, Matsumoto T, Tabara Y, Gozal D, Smith D, Murase K, Tanizawa K, Takahashi N, Nakatsuka Y, Hamada S, Handa T, Takeyama H, Oga T, Nakamoto I, Wakamura T, Komenami N, Setoh K, Tsutsumi T, Kawaguchi T, Kamatani Y, Takahashi Y, Morita S, Nakayama T, Hirai T, Matsuda F, and Chin K

Subjects
Female, Glucose, Humans, Male, Middle Aged, Oximetry, Prevalence, Risk Factors, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Sleep Apnea Syndromes complications, Sleep Apnea Syndromes epidemiology
Abstract

Study Objectives: It is well known that a family history of diabetes (FHD) is a definitive risk factor for type 2 diabetes. It has not been known whether sleep-disordered breathing (SDB) increases the prevalence of diabetes in those with an FHD., Methods: We assessed SDB severity in 7,477 study participants by oximetry corrected by objective sleep duration determined by wrist actigraphy. Glycated hemoglobin ≥6.5% and/or current medication for diabetes indicated the presence of diabetes. In addition to the overall prevalence, the prevalence of recent-onset diabetes during the nearly 5 years before the SDB measurements were made was investigated., Results: Of the 7,477 participants (mean age: 57.9; range: 34.2-80.7; SD: 12.1 years; 67.7% females), 1,569 had an FHD. The prevalence of diabetes in FHD participants with moderate-to-severe SDB (MS-SDB) was higher than in those without SDB (MS-SDB vs without SDB: all, 29.3% vs 3.3% [P < .001]; females, 32.6% vs 1.9% [P < .001]; males, 26.2% vs 11.7% [P = .037]). However, multivariate analysis showed that MS-SDB was significantly associated with a higher prevalence of diabetes only in FHD-positive females (odds ratio [95% confidence interval]: females, 7.43 [3.16-17.45]; males, 0.92 [0.37-2.31]). Among the FHD-positive participants, the prevalence of recent-onset diabetes was higher in those with MS-SDB than those without SDB, but only in females (MS-SDB vs without SDB: 21.4% vs 1.1%; P < 0.001)., Conclusions: MS-SDB was associated with diabetes risk in females with an FHD, and future studies are needed on whether treatment of SDB in females with an FHD would prevent the onset of diabetes., (© 2021 American Academy of Sleep Medicine.)

Published
2021
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42. Association of ALPL variants with serum alkaline phosphatase and bone traits in the general Japanese population: The Nagahama Study.

Author

Nagata M, Setoh K, Takahashi M, Higasa K, Kawaguchi T, Kawasaki H, Wada T, Watanabe A, Sawai H, Tabara Y, Yamada T, Matsuda F, and Kosugi S

Subjects
Adult, Alkaline Phosphatase blood, Bone and Bones metabolism, Bone and Bones pathology, DNA Mutational Analysis, Female, Humans, Hypophosphatasia blood, Hypophosphatasia epidemiology, Hypophosphatasia genetics, Japan epidemiology, Longitudinal Studies, Male, Phenotype, Pregnancy, Whole Genome Sequencing, Alkaline Phosphatase genetics, Bone Density genetics, Bone Development genetics, Genetic Predisposition to Disease
Abstract

Although alkaline phosphatase (ALP) activity is relatively low in carriers of recessive type hypophosphatasia (HPP), most are asymptomatic and therefore do not undergo medical evaluations. We analyzed the association of ALP-encoding ALPL variants with serum ALP and bone traits in the general Japanese population. Study participants (n = 9671) were from the Nagahama Study, which was a longitudinal cohort study of an apparently healthy general Japanese population. ALPL variants were analyzed by whole-genome sequencing or TaqMan probe assays using DNA extracted from peripheral blood samples. The speed of sound in calcaneal bone was assessed by quantitative ultrasound (QUS) and used as surrogate measures of bone mineral density. We identified 13 ALPL variants. Minor allele frequencies of three variants were higher than expected. Variant c.529G > A has been reported as a possible pathogenic variant for adult type HPP. Variants c.979C > T and c.1559delT are reported as pathogenic variants for perinatal severe HPP or infantile HPP. The allele frequencies of c.529G > A, c.979C > T, and c.1559delT were 0.0107, 0.0040, and 0.0014, respectively. Serum ALP activity was significantly lower and differed among the three variants (P < 0.001), as well as between individuals with and without any of the three variants (P < 0.001). Serum ALP activity was inversely associated with QUS values, although no direct association was observed between the ALPL variants and QUS values. An association between serum ALP activity and QUS was confirmed; however, we failed to detect an association between ALPL variants and bone traits in the general Japanese population.

Published
2020
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