@article {382606, title = {Characterization of large structural genetic mosaicism in human autosomes.}, journal = {Am J Hum Genet}, volume = {96}, number = {3}, year = {2015}, month = {2015 Mar 5}, pages = {487-97}, abstract = {Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (\>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total\ GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68\%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73\%] individuals). Restricting to events \>2 Mb in size, we observed an increase in event frequency as event\ size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5\ {\texttimes} 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in\ the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2015.01.011}, author = {Machiela, Mitchell J and Zhou, Weiyin and Sampson, Joshua N and Dean, Michael C and Jacobs, Kevin B and Black, Amanda and Brinton, Louise A and Chang, I-Shou and Chen, Chu and Chen, Constance and Chen, Kexin and Cook, Linda S and Crous Bou, Marta and De Vivo, Immaculata and Doherty, Jennifer and Friedenreich, Christine M and Gaudet, Mia M and Haiman, Christopher A and Hankinson, Susan E and Hartge, Patricia and Henderson, Brian E and Hong, Yun-Chul and Hosgood, H Dean and Hsiung, Chao A and Hu, Wei and Hunter, David J and Jessop, Lea and Kim, Hee Nam and Kim, Yeul Hong and Kim, Young Tae and Klein, Robert and Kraft, Peter and Lan, Qing and Lin, Dongxin and Liu, Jianjun and Le Marchand, Loic and Liang, Xiaolin and Lissowska, Jolanta and Lu, Lingeng and Magliocco, Anthony M and Matsuo, Keitaro and Olson, Sara H and Orlow, Irene and Park, Jae Yong and Pooler, Loreall and Prescott, Jennifer and Rastogi, Radhai and Risch, Harvey A and Schumacher, Fredrick and Seow, Adeline and Setiawan, Veronica Wendy and Shen, Hongbing and Sheng, Xin and Shin, Min-Ho and Shu, Xiao-Ou and Van Den Berg, David and Wang, Jiu-Cun and Wentzensen, Nicolas and Wong, Maria Pik and Wu, Chen and Wu, Tangchun and Wu, Yi-Long and Xia, Lucy and Yang, Hannah P and Yang, Pan-Chyr and Zheng, Wei and Zhou, Baosen and Abnet, Christian C and Albanes, Demetrius and Aldrich, Melinda C and Amos, Christopher and Amundadottir, Laufey T and Berndt, Sonja I and Blot, William J and Bock, Cathryn H and Bracci, Paige M and Burdett, Laurie and Buring, Julie E and Butler, Mary A and Carre{\'o}n, Tania and Chatterjee, Nilanjan and Chung, Charles C and Cook, Michael B and Cullen, Michael and Davis, Faith G and Ding, Ti and Duell, Eric J and Epstein, Caroline G and Fan, Jin-Hu and Figueroa, Jonine D and Fraumeni, Joseph F and Freedman, Neal D and Fuchs, Charles S and Gao, Yu-Tang and Gapstur, Susan M and Pati{\~n}o-Garcia, Ana and Garcia-Closas, Montserrat and Gaziano, J Michael and Giles, Graham G and Gillanders, Elizabeth M and Giovannucci, Edward L and Goldin, Lynn and Goldstein, Alisa M and Greene, Mark H and Hallmans, Goran and Harris, Curtis C and Henriksson, Roger and Holly, Elizabeth A and Hoover, Robert N and Hu, Nan and Hutchinson, Amy and Jenab, Mazda and Johansen, Christoffer and Khaw, Kay-Tee and Koh, Woon-Puay and Kolonel, Laurence N and Kooperberg, Charles and Krogh, Vittorio and Kurtz, Robert C and LaCroix, Andrea and Landgren, Annelie and Landi, Maria Teresa and Li, Donghui and Liao, Linda M and Malats, Nuria and McGlynn, Katherine A and McNeill, Lorna H and McWilliams, Robert R and Melin, Beatrice S and Mirabello, Lisa and Peplonska, Beata and Peters, Ulrike and Petersen, Gloria M and Prokunina-Olsson, Ludmila and Purdue, Mark and Qiao, You-Lin and Rabe, Kari G and Rajaraman, Preetha and Real, Francisco X and Riboli, Elio and Rodr{\'\i}guez-Santiago, Benjam{\'\i}n and Rothman, Nathaniel and Ruder, Avima M and Savage, Sharon A and Schwartz, Ann G and Schwartz, Kendra L and Sesso, Howard D and Severi, Gianluca and Silverman, Debra T and Spitz, Margaret R and Stevens, Victoria L and Stolzenberg-Solomon, Rachael and Stram, Daniel and Tang, Ze-Zhong and Taylor, Philip R and Teras, Lauren R and Tobias, Geoffrey S and Viswanathan, Kala and Wacholder, Sholom and Wang, Zhaoming and Weinstein, Stephanie J and Wheeler, William and White, Emily and Wiencke, John K and Wolpin, Brian M and Wu, Xifeng and Wunder, Jay S and Yu, Kai and Zanetti, Krista A and Zeleniuch-Jacquotte, Anne and Ziegler, Regina G and deAndrade, Mariza and Barnes, Kathleen C and Beaty, Terri H and Bierut, Laura J and Desch, Karl C and Doheny, Kimberly F and Feenstra, Bjarke and Ginsburg, David and Heit, John A and Kang, Jae H and Laurie, Cecilia A and Li, Jun Z and Lowe, William L and Marazita, Mary L and Melbye, Mads and Mirel, Daniel B and Murray, Jeffrey C and Nelson, Sarah C and Pasquale, Louis R and Rice, Kenneth and Wiggs, Janey L and Wise, Anastasia and Tucker, Margaret and P{\'e}rez-Jurado, Luis A and Laurie, Cathy C and Caporaso, Neil E and Yeager, Meredith and Chanock, Stephen J} }