Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Mitchell J. MacHiela; Weiyin Zhou; Eric Karlins; Joshua N. Sampson; Neal D. Freedman; Qi Yang; Belynda Hicks; Casey Dagnall; Christopher Hautman; Kevin B. Jacobs; Christian C. Abnet; Melinda C. Aldrich; Christopher Amos; Laufey T. Amundadottir; Alan A. Arslan; Laura E. Beane-Freeman; Sonja I. Berndt; Amanda Black; William J. Blot; Cathryn H. Bock; Paige M. Bracci; Louise A. Brinton; H. Bas Bueno-De-Mesquita; Laurie Burdett; Julie E. Buring; Mary A. Butler; Federico Canzian; Tania Carreón; Kari G. Chaffee; I. Shou Chang; Nilanjan Chatterjee; Chu Chen; Constance Chen; Kexin Chen; Charles C. Chung; Linda S. Cook; Marta Crous Bou; Michael Cullen; Faith G. Davis; Immaculata De Vivo; Ti Ding; Jennifer Doherty; Eric J. Duell; Caroline G. Epstein; Jin Hu Fan; Jonine D. Figueroa; Joseph F. Fraumeni; Christine M. Friedenreich; Charles S. Fuchs; Steven Gallinger; Yu Tang Gao; Susan M. Gapstur; Montserrat Garcia-Closas; Mia M. Gaudet; J. Michael Gaziano; Graham G. Giles; Elizabeth M. Gillanders; Edward L. Giovannucci; Lynn Goldin; Alisa M. Goldstein; Christopher A. Haiman; Goran Hallmans; Susan E. Hankinson; Curtis C. Harris; Roger Henriksson; Elizabeth A. Holly; Yun Chul Hong; Robert N. Hoover; Chao A. Hsiung; Nan Hu; Wei Hu; David J. Hunter; Amy Hutchinson; Mazda Jenab; Christoffer Johansen; Kay Tee Khaw; Hee Nam Kim; Yeul Hong Kim; Young Tae Kim; Alison P. Klein; Robert Klein; Woon Puay Koh; Laurence N. Kolonel; Charles Kooperberg; Peter Kraft; Vittorio Krogh; Robert C. Kurtz; Andrea Lacroix; Qing Lan; Maria Teresa Landi; Loic Le Marchand; Donghui Li; Xiaolin Liang; Linda M. Liao; Dongxin Lin; Jianjun Liu; Jolanta Lissowska; Lingeng Lu; Anthony M. Magliocco; Nuria Malats; Keitaro Matsuo; Lorna H. McNeill; Robert R. McWilliams; Beatrice S. Melin; Lisa Mirabello; Lee Moore; Sara H. Olson; Irene Orlow; Jae Yong Park; Ana Patinõ-Garcia; Beata Peplonska; Ulrike Peters; Gloria M. Petersen; Loreall Pooler; Jennifer Prescott; Ludmila Prokunina-Olsson; Mark P. Purdue; You Lin Qiao; Preetha Rajaraman; Francisco X. Real; Elio Riboli; Harvey A. Risch; Benjamin Rodriguez-Santiago; Avima M. Ruder; Sharon A. Savage; Fredrick Schumacher; Ann G. Schwartz; Kendra L. Schwartz; Adeline Seow; Veronica Wendy Setiawan; Gianluca Severi; Hongbing Shen; Xin Sheng; Min Ho Shin; Xiao Ou Shu; Debra T. Silverman; Margaret R. Spitz; Victoria L. Stevens; Rachael Stolzenberg-Solomon; Daniel Stram; Ze Zhong Tang; Philip R. Taylor; Lauren R. Teras; Geoffrey S. Tobias; David Van Den Berg; Kala Visvanathan; Sholom Wacholder; Jiu Cun Wang; Zhaoming Wang; Nicolas Wentzensen; William Wheeler; Emily White; John K. Wiencke; Brian M. Wolpin; Maria Pik Wong; Chen Wu; Tangchun Wu; Xifeng Wu; Yi Long Wu; Jay S. Wunder; Lucy Xia; Hannah P. Yang; Pan Chyr Yang; Kai Yu; Krista A. Zanetti; Anne Zeleniuch-Jacquotte; Wei Zheng; Baosen Zhou; Regina G. Ziegler; Luis A. Perez-Jurado; Neil E. Caporaso; Nathaniel Rothman; Margaret Tucker; Michael C. Dean; Meredith Yeager; Stephen J. Chanock

doi:10.1038/ncomms11843

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Mitchell J. MacHiela, Weiyin Zhou, Eric Karlins, Joshua N. Sampson, Neal D. Freedman, Qi Yang, Belynda Hicks, Casey Dagnall, Christopher Hautman, Kevin B. Jacobs, Christian C. Abnet, Melinda C. Aldrich, Christopher Amos, Laufey T. Amundadottir, Alan A. Arslan, Laura E. Beane-Freeman, Sonja I. Berndt, Amanda Black, William J. Blot, Cathryn H. BockPaige M. Bracci, Louise A. Brinton, H. Bas Bueno-De-Mesquita, Laurie Burdett, Julie E. Buring, Mary A. Butler, Federico Canzian, Tania Carreón, Kari G. Chaffee, I. Shou Chang, Nilanjan Chatterjee, Chu Chen, Constance Chen, Kexin Chen, Charles C. Chung, Linda S. Cook, Marta Crous Bou, Michael Cullen, Faith G. Davis, Immaculata De Vivo, Ti Ding, Jennifer Doherty, Eric J. Duell, Caroline G. Epstein, Jin Hu Fan, Jonine D. Figueroa, Joseph F. Fraumeni, Christine M. Friedenreich, Charles S. Fuchs, Steven Gallinger, Yu Tang Gao, Susan M. Gapstur, Montserrat Garcia-Closas, Mia M. Gaudet, J. Michael Gaziano, Graham G. Giles, Elizabeth M. Gillanders, Edward L. Giovannucci, Lynn Goldin, Alisa M. Goldstein, Christopher A. Haiman, Goran Hallmans, Susan E. Hankinson, Curtis C. Harris, Roger Henriksson, Elizabeth A. Holly, Yun Chul Hong, Robert N. Hoover, Chao A. Hsiung, Nan Hu, Wei Hu, David J. Hunter, Amy Hutchinson, Mazda Jenab, Christoffer Johansen, Kay Tee Khaw, Hee Nam Kim, Yeul Hong Kim, Young Tae Kim, Alison P. Klein, Robert Klein, Woon Puay Koh, Laurence N. Kolonel, Charles Kooperberg, Peter Kraft, Vittorio Krogh, Robert C. Kurtz, Andrea Lacroix, Qing Lan, Maria Teresa Landi, Loic Le Marchand, Donghui Li, Xiaolin Liang, Linda M. Liao, Dongxin Lin, Jianjun Liu, Jolanta Lissowska, Lingeng Lu, Anthony M. Magliocco, Nuria Malats, Keitaro Matsuo, Lorna H. McNeill, Robert R. McWilliams, Beatrice S. Melin, Lisa Mirabello, Lee Moore, Sara H. Olson, Irene Orlow, Jae Yong Park, Ana Patinõ-Garcia, Beata Peplonska, Ulrike Peters, Gloria M. Petersen, Loreall Pooler, Jennifer Prescott, Ludmila Prokunina-Olsson, Mark P. Purdue, You Lin Qiao, Preetha Rajaraman, Francisco X. Real, Elio Riboli, Harvey A. Risch, Benjamin Rodriguez-Santiago, Avima M. Ruder, Sharon A. Savage, Fredrick Schumacher, Ann G. Schwartz, Kendra L. Schwartz, Adeline Seow, Veronica Wendy Setiawan, Gianluca Severi, Hongbing Shen, Xin Sheng, Min Ho Shin, Xiao Ou Shu, Debra T. Silverman, Margaret R. Spitz, Victoria L. Stevens, Rachael Stolzenberg-Solomon, Daniel Stram, Ze Zhong Tang, Philip R. Taylor, Lauren R. Teras, Geoffrey S. Tobias, David Van Den Berg, Kala Visvanathan, Sholom Wacholder, Jiu Cun Wang, Zhaoming Wang, Nicolas Wentzensen, William Wheeler, Emily White, John K. Wiencke, Brian M. Wolpin, Maria Pik Wong, Chen Wu, Tangchun Wu, Xifeng Wu, Yi Long Wu, Jay S. Wunder, Lucy Xia, Hannah P. Yang, Pan Chyr Yang, Kai Yu, Krista A. Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Regina G. Ziegler, Luis A. Perez-Jurado, Neil E. Caporaso, Nathaniel Rothman, Margaret Tucker, Michael C. Dean, Meredith Yeager, Stephen J. Chanock

Research output: Contribution to journal › Article › peer-review

92 Citations (Scopus)

Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Original language	English
Article number	11843
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11843
Publication status	Published - 2016 Jun 13

Bibliographical note

Funding Information:
Center for Genotyping and Analysis (U01HG04424); Cancer Prevention Study-II (American Cancer Society); Center for Inherited Disease Research (U01HG004438, HHSN268200782096C); Endometrial cancer (R01 CA 134958); Fred Hutchinson Cancer Research Center (funds from the Fred Hutchinson Cancer Research Center and National Institute of Health grants (R35 CA 39779, RO1 CA 75977, RO3 CA 80636, N01 HD 2 3166, K05 CA 92002, CA 105212 and R01 CA87538)); Fudan Lung Cancer Study (Ministry of Health (201002007); Ministry of Science and Technology (2011BAI09B00); National S&T Major Special Project (2011ZX09102-010-01); China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518); National Science Foundation of China (30890034); National Basic Research Program (2012CB944600); Scientific and Technological Support Plans from Jiangsu Province (BE2010715)); Gene-Environment Association Studies (Coordinating Center:U01 HG004446, Manuscript preparation: P01-GM099568); Genes and Environment in Lung Cancer, Singapore Study (National Medical Research Council Singapore grant.

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms11843

Cite this

MacHiela, M. J., Zhou, W., Karlins, E., Sampson, J. N., Freedman, N. D., Yang, Q., Hicks, B., Dagnall, C., Hautman, C., Jacobs, K. B., Abnet, C. C., Aldrich, M. C., Amos, C., Amundadottir, L. T., Arslan, A. A., Beane-Freeman, L. E., Berndt, S. I., Black, A., Blot, W. J., ... Chanock, S. J. (2016). Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nature communications, 7, Article 11843. https://doi.org/10.1038/ncomms11843

MacHiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-De-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreón, T, Chaffee, KG, Chang, IS, Chatterjee, N, Chen, C, Chen, C, Chen, K, Chung, CC, Cook, LS, Crous Bou, M, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, JH, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, YT, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, YC, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, KT, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, WP, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, Lacroix, A, Lan, Q, Landi, MT, Marchand, LL, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patinõ-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, YL, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Wendy Setiawan, V, Severi, G, Shen, H, Sheng, X, Shin, MH, Shu, XO, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, ZZ, Taylor, PR, Teras, LR, Tobias, GS, Van Den Berg, D, Visvanathan, K, Wacholder, S, Wang, JC, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, YL, Wunder, JS, Xia, L, Yang, HP, Yang, PC, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M & Chanock, SJ 2016, 'Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome', Nature communications, vol. 7, 11843. https://doi.org/10.1038/ncomms11843

@article{5640445ca8594fdd89f2d52b29619fd5,

title = "Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome",

abstract = "To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.",

author = "MacHiela, {Mitchell J.} and Weiyin Zhou and Eric Karlins and Sampson, {Joshua N.} and Freedman, {Neal D.} and Qi Yang and Belynda Hicks and Casey Dagnall and Christopher Hautman and Jacobs, {Kevin B.} and Abnet, {Christian C.} and Aldrich, {Melinda C.} and Christopher Amos and Amundadottir, {Laufey T.} and Arslan, {Alan A.} and Beane-Freeman, {Laura E.} and Berndt, {Sonja I.} and Amanda Black and Blot, {William J.} and Bock, {Cathryn H.} and Bracci, {Paige M.} and Brinton, {Louise A.} and Bueno-De-Mesquita, {H. Bas} and Laurie Burdett and Buring, {Julie E.} and Butler, {Mary A.} and Federico Canzian and Tania Carre{\'o}n and Chaffee, {Kari G.} and Chang, {I. Shou} and Nilanjan Chatterjee and Chu Chen and Constance Chen and Kexin Chen and Chung, {Charles C.} and Cook, {Linda S.} and {Crous Bou}, Marta and Michael Cullen and Davis, {Faith G.} and {De Vivo}, Immaculata and Ti Ding and Jennifer Doherty and Duell, {Eric J.} and Epstein, {Caroline G.} and Fan, {Jin Hu} and Figueroa, {Jonine D.} and Fraumeni, {Joseph F.} and Friedenreich, {Christine M.} and Fuchs, {Charles S.} and Steven Gallinger and Gao, {Yu Tang} and Gapstur, {Susan M.} and Montserrat Garcia-Closas and Gaudet, {Mia M.} and Gaziano, {J. Michael} and Giles, {Graham G.} and Gillanders, {Elizabeth M.} and Giovannucci, {Edward L.} and Lynn Goldin and Goldstein, {Alisa M.} and Haiman, {Christopher A.} and Goran Hallmans and Hankinson, {Susan E.} and Harris, {Curtis C.} and Roger Henriksson and Holly, {Elizabeth A.} and Hong, {Yun Chul} and Hoover, {Robert N.} and Hsiung, {Chao A.} and Nan Hu and Wei Hu and Hunter, {David J.} and Amy Hutchinson and Mazda Jenab and Christoffer Johansen and Khaw, {Kay Tee} and Kim, {Hee Nam} and Kim, {Yeul Hong} and Kim, {Young Tae} and Klein, {Alison P.} and Robert Klein and Koh, {Woon Puay} and Kolonel, {Laurence N.} and Charles Kooperberg and Peter Kraft and Vittorio Krogh and Kurtz, {Robert C.} and Andrea Lacroix and Qing Lan and Landi, {Maria Teresa} and Marchand, {Loic Le} and Donghui Li and Xiaolin Liang and Liao, {Linda M.} and Dongxin Lin and Jianjun Liu and Jolanta Lissowska and Lingeng Lu and Magliocco, {Anthony M.} and Nuria Malats and Keitaro Matsuo and McNeill, {Lorna H.} and McWilliams, {Robert R.} and Melin, {Beatrice S.} and Lisa Mirabello and Lee Moore and Olson, {Sara H.} and Irene Orlow and Park, {Jae Yong} and Ana Patin{\~o}-Garcia and Beata Peplonska and Ulrike Peters and Petersen, {Gloria M.} and Loreall Pooler and Jennifer Prescott and Ludmila Prokunina-Olsson and Purdue, {Mark P.} and Qiao, {You Lin} and Preetha Rajaraman and Real, {Francisco X.} and Elio Riboli and Risch, {Harvey A.} and Benjamin Rodriguez-Santiago and Ruder, {Avima M.} and Savage, {Sharon A.} and Fredrick Schumacher and Schwartz, {Ann G.} and Schwartz, {Kendra L.} and Adeline Seow and {Wendy Setiawan}, Veronica and Gianluca Severi and Hongbing Shen and Xin Sheng and Shin, {Min Ho} and Shu, {Xiao Ou} and Silverman, {Debra T.} and Spitz, {Margaret R.} and Stevens, {Victoria L.} and Rachael Stolzenberg-Solomon and Daniel Stram and Tang, {Ze Zhong} and Taylor, {Philip R.} and Teras, {Lauren R.} and Tobias, {Geoffrey S.} and {Van Den Berg}, David and Kala Visvanathan and Sholom Wacholder and Wang, {Jiu Cun} and Zhaoming Wang and Nicolas Wentzensen and William Wheeler and Emily White and Wiencke, {John K.} and Wolpin, {Brian M.} and Wong, {Maria Pik} and Chen Wu and Tangchun Wu and Xifeng Wu and Wu, {Yi Long} and Wunder, {Jay S.} and Lucy Xia and Yang, {Hannah P.} and Yang, {Pan Chyr} and Kai Yu and Zanetti, {Krista A.} and Anne Zeleniuch-Jacquotte and Wei Zheng and Baosen Zhou and Ziegler, {Regina G.} and Perez-Jurado, {Luis A.} and Caporaso, {Neil E.} and Nathaniel Rothman and Margaret Tucker and Dean, {Michael C.} and Meredith Yeager and Chanock, {Stephen J.}",

note = "Funding Information: Center for Genotyping and Analysis (U01HG04424); Cancer Prevention Study-II (American Cancer Society); Center for Inherited Disease Research (U01HG004438, HHSN268200782096C); Endometrial cancer (R01 CA 134958); Fred Hutchinson Cancer Research Center (funds from the Fred Hutchinson Cancer Research Center and National Institute of Health grants (R35 CA 39779, RO1 CA 75977, RO3 CA 80636, N01 HD 2 3166, K05 CA 92002, CA 105212 and R01 CA87538)); Fudan Lung Cancer Study (Ministry of Health (201002007); Ministry of Science and Technology (2011BAI09B00); National S&T Major Special Project (2011ZX09102-010-01); China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518); National Science Foundation of China (30890034); National Basic Research Program (2012CB944600); Scientific and Technological Support Plans from Jiangsu Province (BE2010715)); Gene-Environment Association Studies (Coordinating Center:U01 HG004446, Manuscript preparation: P01-GM099568); Genes and Environment in Lung Cancer, Singapore Study (National Medical Research Council Singapore grant.",

year = "2016",

month = jun,

day = "13",

doi = "10.1038/ncomms11843",

language = "English",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

AU - MacHiela, Mitchell J.

AU - Zhou, Weiyin

AU - Karlins, Eric

AU - Sampson, Joshua N.

AU - Freedman, Neal D.

AU - Yang, Qi

AU - Hicks, Belynda

AU - Dagnall, Casey

AU - Hautman, Christopher

AU - Jacobs, Kevin B.

AU - Abnet, Christian C.

AU - Aldrich, Melinda C.

AU - Amos, Christopher

AU - Amundadottir, Laufey T.

AU - Arslan, Alan A.

AU - Beane-Freeman, Laura E.

AU - Berndt, Sonja I.

AU - Black, Amanda

AU - Blot, William J.

AU - Bock, Cathryn H.

AU - Bracci, Paige M.

AU - Brinton, Louise A.

AU - Bueno-De-Mesquita, H. Bas

AU - Burdett, Laurie

AU - Buring, Julie E.

AU - Butler, Mary A.

AU - Canzian, Federico

AU - Carreón, Tania

AU - Chaffee, Kari G.

AU - Chang, I. Shou

AU - Chatterjee, Nilanjan

AU - Chen, Chu

AU - Chen, Constance

AU - Chen, Kexin

AU - Chung, Charles C.

AU - Cook, Linda S.

AU - Crous Bou, Marta

AU - Cullen, Michael

AU - Davis, Faith G.

AU - De Vivo, Immaculata

AU - Ding, Ti

AU - Doherty, Jennifer

AU - Duell, Eric J.

AU - Epstein, Caroline G.

AU - Fan, Jin Hu

AU - Figueroa, Jonine D.

AU - Fraumeni, Joseph F.

AU - Friedenreich, Christine M.

AU - Fuchs, Charles S.

AU - Gallinger, Steven

AU - Gao, Yu Tang

AU - Gapstur, Susan M.

AU - Garcia-Closas, Montserrat

AU - Gaudet, Mia M.

AU - Gaziano, J. Michael

AU - Giles, Graham G.

AU - Gillanders, Elizabeth M.

AU - Giovannucci, Edward L.

AU - Goldin, Lynn

AU - Goldstein, Alisa M.

AU - Haiman, Christopher A.

AU - Hallmans, Goran

AU - Hankinson, Susan E.

AU - Harris, Curtis C.

AU - Henriksson, Roger

AU - Holly, Elizabeth A.

AU - Hong, Yun Chul

AU - Hoover, Robert N.

AU - Hsiung, Chao A.

AU - Hu, Nan

AU - Hu, Wei

AU - Hunter, David J.

AU - Hutchinson, Amy

AU - Jenab, Mazda

AU - Johansen, Christoffer

AU - Khaw, Kay Tee

AU - Kim, Hee Nam

AU - Kim, Yeul Hong

AU - Kim, Young Tae

AU - Klein, Alison P.

AU - Klein, Robert

AU - Koh, Woon Puay

AU - Kolonel, Laurence N.

AU - Kooperberg, Charles

AU - Kraft, Peter

AU - Krogh, Vittorio

AU - Kurtz, Robert C.

AU - Lacroix, Andrea

AU - Lan, Qing

AU - Landi, Maria Teresa

AU - Marchand, Loic Le

AU - Li, Donghui

AU - Liang, Xiaolin

AU - Liao, Linda M.

AU - Lin, Dongxin

AU - Liu, Jianjun

AU - Lissowska, Jolanta

AU - Lu, Lingeng

AU - Magliocco, Anthony M.

AU - Malats, Nuria

AU - Matsuo, Keitaro

AU - McNeill, Lorna H.

AU - McWilliams, Robert R.

AU - Melin, Beatrice S.

AU - Mirabello, Lisa

AU - Moore, Lee

AU - Olson, Sara H.

AU - Orlow, Irene

AU - Park, Jae Yong

AU - Patinõ-Garcia, Ana

AU - Peplonska, Beata

AU - Peters, Ulrike

AU - Petersen, Gloria M.

AU - Pooler, Loreall

AU - Prescott, Jennifer

AU - Prokunina-Olsson, Ludmila

AU - Purdue, Mark P.

AU - Qiao, You Lin

AU - Rajaraman, Preetha

AU - Real, Francisco X.

AU - Riboli, Elio

AU - Risch, Harvey A.

AU - Rodriguez-Santiago, Benjamin

AU - Ruder, Avima M.

AU - Savage, Sharon A.

AU - Schumacher, Fredrick

AU - Schwartz, Ann G.

AU - Schwartz, Kendra L.

AU - Seow, Adeline

AU - Wendy Setiawan, Veronica

AU - Severi, Gianluca

AU - Shen, Hongbing

AU - Sheng, Xin

AU - Shin, Min Ho

AU - Shu, Xiao Ou

AU - Silverman, Debra T.

AU - Spitz, Margaret R.

AU - Stevens, Victoria L.

AU - Stolzenberg-Solomon, Rachael

AU - Stram, Daniel

AU - Tang, Ze Zhong

AU - Taylor, Philip R.

AU - Teras, Lauren R.

AU - Tobias, Geoffrey S.

AU - Van Den Berg, David

AU - Visvanathan, Kala

AU - Wacholder, Sholom

AU - Wang, Jiu Cun

AU - Wang, Zhaoming

AU - Wentzensen, Nicolas

AU - Wheeler, William

AU - White, Emily

AU - Wiencke, John K.

AU - Wolpin, Brian M.

AU - Wong, Maria Pik

AU - Wu, Chen

AU - Wu, Tangchun

AU - Wu, Xifeng

AU - Wu, Yi Long

AU - Wunder, Jay S.

AU - Xia, Lucy

AU - Yang, Hannah P.

AU - Yang, Pan Chyr

AU - Yu, Kai

AU - Zanetti, Krista A.

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Zhou, Baosen

AU - Ziegler, Regina G.

AU - Perez-Jurado, Luis A.

AU - Caporaso, Neil E.

AU - Rothman, Nathaniel

AU - Tucker, Margaret

AU - Dean, Michael C.

AU - Yeager, Meredith

AU - Chanock, Stephen J.

N1 - Funding Information: Center for Genotyping and Analysis (U01HG04424); Cancer Prevention Study-II (American Cancer Society); Center for Inherited Disease Research (U01HG004438, HHSN268200782096C); Endometrial cancer (R01 CA 134958); Fred Hutchinson Cancer Research Center (funds from the Fred Hutchinson Cancer Research Center and National Institute of Health grants (R35 CA 39779, RO1 CA 75977, RO3 CA 80636, N01 HD 2 3166, K05 CA 92002, CA 105212 and R01 CA87538)); Fudan Lung Cancer Study (Ministry of Health (201002007); Ministry of Science and Technology (2011BAI09B00); National S&T Major Special Project (2011ZX09102-010-01); China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518); National Science Foundation of China (30890034); National Basic Research Program (2012CB944600); Scientific and Technological Support Plans from Jiangsu Province (BE2010715)); Gene-Environment Association Studies (Coordinating Center:U01 HG004446, Manuscript preparation: P01-GM099568); Genes and Environment in Lung Cancer, Singapore Study (National Medical Research Council Singapore grant.

PY - 2016/6/13

Y1 - 2016/6/13

N2 - To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

AB - To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

UR - http://www.scopus.com/inward/record.url?scp=84974736225&partnerID=8YFLogxK

U2 - 10.1038/ncomms11843

DO - 10.1038/ncomms11843

M3 - Article

C2 - 27291797

AN - SCOPUS:84974736225

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 11843

ER -

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

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UN SDGs

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