| Literature DB >> 25748358 |
Mitchell J Machiela1, Weiyin Zhou2, Joshua N Sampson1, Michael C Dean3, Kevin B Jacobs4, Amanda Black1, Louise A Brinton1, I-Shou Chang5, Chu Chen6, Constance Chen7, Kexin Chen8, Linda S Cook9, Marta Crous Bou10, Immaculata De Vivo10, Jennifer Doherty11, Christine M Friedenreich12, Mia M Gaudet13, Christopher A Haiman14, Susan E Hankinson15, Patricia Hartge1, Brian E Henderson14, Yun-Chul Hong16, H Dean Hosgood17, Chao A Hsiung18, Wei Hu1, David J Hunter19, Lea Jessop1, Hee Nam Kim20, Yeul Hong Kim21, Young Tae Kim22, Robert Klein23, Peter Kraft7, Qing Lan1, Dongxin Lin24, Jianjun Liu25, Loic Le Marchand26, Xiaolin Liang27, Jolanta Lissowska28, Lingeng Lu29, Anthony M Magliocco30, Keitaro Matsuo31, Sara H Olson27, Irene Orlow27, Jae Yong Park32, Loreall Pooler33, Jennifer Prescott10, Radhai Rastogi27, Harvey A Risch29, Fredrick Schumacher14, Adeline Seow34, Veronica Wendy Setiawan14, Hongbing Shen35, Xin Sheng33, Min-Ho Shin36, Xiao-Ou Shu37, David VanDen Berg14, Jiu-Cun Wang38, Nicolas Wentzensen1, Maria Pik Wong39, Chen Wu24, Tangchun Wu40, Yi-Long Wu41, Lucy Xia33, Hannah P Yang1, Pan-Chyr Yang42, Wei Zheng43, Baosen Zhou44, Christian C Abnet1, Demetrius Albanes1, Melinda C Aldrich45, Christopher Amos46, Laufey T Amundadottir1, Sonja I Berndt1, William J Blot47, Cathryn H Bock48, Paige M Bracci49, Laurie Burdett2, Julie E Buring50, Mary A Butler51, Tania Carreón51, Nilanjan Chatterjee1, Charles C Chung2, Michael B Cook1, Michael Cullen2, Faith G Davis52, Ti Ding53, Eric J Duell54, Caroline G Epstein1, Jin-Hu Fan55, Jonine D Figueroa1, Joseph F Fraumeni1, Neal D Freedman1, Charles S Fuchs56, Yu-Tang Gao57, Susan M Gapstur13, Ana Patiño-Garcia58, Montserrat Garcia-Closas59, J Michael Gaziano60, Graham G Giles61, Elizabeth M Gillanders62, Edward L Giovannucci63, Lynn Goldin1, Alisa M Goldstein1, Mark H Greene1, Goran Hallmans64, Curtis C Harris65, Roger Henriksson66, Elizabeth A Holly49, Robert N Hoover1, Nan Hu1, Amy Hutchinson2, Mazda Jenab67, Christoffer Johansen68, Kay-Tee Khaw69, Woon-Puay Koh70, Laurence N Kolonel26, Charles Kooperberg6, Vittorio Krogh71, Robert C Kurtz72, Andrea LaCroix6, Annelie Landgren1, Maria Teresa Landi1, Donghui Li73, Linda M Liao1, Nuria Malats74, Katherine A McGlynn1, Lorna H McNeill75, Robert R McWilliams76, Beatrice S Melin66, Lisa Mirabello1, Beata Peplonska77, Ulrike Peters6, Gloria M Petersen78, Ludmila Prokunina-Olsson1, Mark Purdue1, You-Lin Qiao79, Kari G Rabe78, Preetha Rajaraman1, Francisco X Real80, Elio Riboli81, Benjamín Rodríguez-Santiago82, Nathaniel Rothman1, Avima M Ruder51, Sharon A Savage1, Ann G Schwartz48, Kendra L Schwartz83, Howard D Sesso50, Gianluca Severi84, Debra T Silverman1, Margaret R Spitz85, Victoria L Stevens13, Rachael Stolzenberg-Solomon1, Daniel Stram14, Ze-Zhong Tang53, Philip R Taylor1, Lauren R Teras13, Geoffrey S Tobias1, Kala Viswanathan86, Sholom Wacholder1, Zhaoming Wang2, Stephanie J Weinstein1, William Wheeler87, Emily White6, John K Wiencke88, Brian M Wolpin56, Xifeng Wu89, Jay S Wunder90, Kai Yu1, Krista A Zanetti62, Anne Zeleniuch-Jacquotte91, Regina G Ziegler1, Mariza de Andrade78, Kathleen C Barnes92, Terri H Beaty86, Laura J Bierut93, Karl C Desch94, Kimberly F Doheny95, Bjarke Feenstra96, David Ginsburg97, John A Heit98, Jae H Kang99, Cecilia A Laurie100, Jun Z Li101, William L Lowe102, Mary L Marazita103, Mads Melbye104, Daniel B Mirel105, Jeffrey C Murray106, Sarah C Nelson100, Louis R Pasquale107, Kenneth Rice100, Janey L Wiggs108, Anastasia Wise109, Margaret Tucker1, Luis A Pérez-Jurado110, Cathy C Laurie100, Neil E Caporaso1, Meredith Yeager2, Stephen J Chanock111.
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 × 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.Entities:
Mesh：
Year: 2015 PMID： 25748358 PMCID： PMC4375431 DOI： 10.1016/j.ajhg.2015.01.011
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025