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.
| Original language | English |
|---|---|
| Pages (from-to) | 487-497 |
| Number of pages | 11 |
| Journal | American Journal of Human Genetics |
| Volume | 96 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 Mar 5 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
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Characterization of large structural genetic mosaicism in human autosomes. / Machiela, Mitchell J.; Zhou, Weiyin; Sampson, Joshua N.; Dean, Michael C.; Jacobs, Kevin B.; Black, Amanda; Brinton, Louise A.; Chang, I. Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S.; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M.; Gaudet, Mia M.; Haiman, Christopher A.; Hankinson, Susan E.; Hartge, Patricia; Henderson, Brian E.; Hong, Yun Chul; Hosgood, H. Dean; Hsiung, Chao A.; Hu, Wei; Hunter, David J.; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Matsuo, Keitaro; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A.; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min Ho; Shu, Xiao Ou; Vanden Berg, David; Wang, Jiu Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi Long; Xia, Lucy; Yang, Hannah P.; Yang, Pan Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C.; Albanes, Demetrius; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Berndt, Sonja I.; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C.; Cook, Michael B.; Cullen, Michael; Davis, Faith G.; Ding, Ti; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Freedman, Neal D.; Fuchs, Charles S.; Gao, Yu Tang; Gapstur, Susan M.; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Greene, Mark H.; Hallmans, Goran; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hoover, Robert N.; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay Tee; Koh, Woon Puay; Kolonel, Laurence N.; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; Lacroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M.; Malats, Nuria; McGlynn, Katherine A.; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You Lin; Rabe, Kari G.; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M.; Savage, Sharon A.; Schwartz, Ann G.; Schwartz, Kendra L.; Sesso, Howard D.; Severi, Gianluca; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J.; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wu, Xifeng; Wunder, Jay S.; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G.; De Andrade, Mariza; Barnes, Kathleen C.; Beaty, Terri H.; Bierut, Laura J.; Desch, Karl C.; Doheny, Kimberly F.; Feenstra, Bjarke; Ginsburg, David; Heit, John A.; Kang, Jae H.; Laurie, Cecilia A.; Li, Jun Z.; Lowe, William L.; Marazita, Mary L.; Melbye, Mads; Mirel, Daniel B.; Murray, Jeffrey C.; Nelson, Sarah C.; Pasquale, Louis R.; Rice, Kenneth; Wiggs, Janey L.; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A.; Laurie, Cathy C.; Caporaso, Neil E.; Yeager, Meredith; Chanock, Stephen J.
In: American Journal of Human Genetics, Vol. 96, No. 3, 05.03.2015, p. 487-497.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of large structural genetic mosaicism in human autosomes
AU - Machiela, Mitchell J.
AU - Zhou, Weiyin
AU - Sampson, Joshua N.
AU - Dean, Michael C.
AU - Jacobs, Kevin B.
AU - Black, Amanda
AU - Brinton, Louise A.
AU - Chang, I. Shou
AU - Chen, Chu
AU - Chen, Constance
AU - Chen, Kexin
AU - Cook, Linda S.
AU - Crous Bou, Marta
AU - De Vivo, Immaculata
AU - Doherty, Jennifer
AU - Friedenreich, Christine M.
AU - Gaudet, Mia M.
AU - Haiman, Christopher A.
AU - Hankinson, Susan E.
AU - Hartge, Patricia
AU - Henderson, Brian E.
AU - Hong, Yun Chul
AU - Hosgood, H. Dean
AU - Hsiung, Chao A.
AU - Hu, Wei
AU - Hunter, David J.
AU - Jessop, Lea
AU - Kim, Hee Nam
AU - Kim, Yeul Hong
AU - Kim, Young Tae
AU - Klein, Robert
AU - Kraft, Peter
AU - Lan, Qing
AU - Lin, Dongxin
AU - Liu, Jianjun
AU - Le Marchand, Loic
AU - Liang, Xiaolin
AU - Lissowska, Jolanta
AU - Lu, Lingeng
AU - Magliocco, Anthony M.
AU - Matsuo, Keitaro
AU - Olson, Sara H.
AU - Orlow, Irene
AU - Park, Jae Yong
AU - Pooler, Loreall
AU - Prescott, Jennifer
AU - Rastogi, Radhai
AU - Risch, Harvey A.
AU - Schumacher, Fredrick
AU - Seow, Adeline
AU - Setiawan, Veronica Wendy
AU - Shen, Hongbing
AU - Sheng, Xin
AU - Shin, Min Ho
AU - Shu, Xiao Ou
AU - Vanden Berg, David
AU - Wang, Jiu Cun
AU - Wentzensen, Nicolas
AU - Wong, Maria Pik
AU - Wu, Chen
AU - Wu, Tangchun
AU - Wu, Yi Long
AU - Xia, Lucy
AU - Yang, Hannah P.
AU - Yang, Pan Chyr
AU - Zheng, Wei
AU - Zhou, Baosen
AU - Abnet, Christian C.
AU - Albanes, Demetrius
AU - Aldrich, Melinda C.
AU - Amos, Christopher
AU - Amundadottir, Laufey T.
AU - Berndt, Sonja I.
AU - Blot, William J.
AU - Bock, Cathryn H.
AU - Bracci, Paige M.
AU - Burdett, Laurie
AU - Buring, Julie E.
AU - Butler, Mary A.
AU - Carreón, Tania
AU - Chatterjee, Nilanjan
AU - Chung, Charles C.
AU - Cook, Michael B.
AU - Cullen, Michael
AU - Davis, Faith G.
AU - Ding, Ti
AU - Duell, Eric J.
AU - Epstein, Caroline G.
AU - Fan, Jin Hu
AU - Figueroa, Jonine D.
AU - Fraumeni, Joseph F.
AU - Freedman, Neal D.
AU - Fuchs, Charles S.
AU - Gao, Yu Tang
AU - Gapstur, Susan M.
AU - Patiño-Garcia, Ana
AU - Garcia-Closas, Montserrat
AU - Gaziano, J. Michael
AU - Giles, Graham G.
AU - Gillanders, Elizabeth M.
AU - Giovannucci, Edward L.
AU - Goldin, Lynn
AU - Goldstein, Alisa M.
AU - Greene, Mark H.
AU - Hallmans, Goran
AU - Harris, Curtis C.
AU - Henriksson, Roger
AU - Holly, Elizabeth A.
AU - Hoover, Robert N.
AU - Hu, Nan
AU - Hutchinson, Amy
AU - Jenab, Mazda
AU - Johansen, Christoffer
AU - Khaw, Kay Tee
AU - Koh, Woon Puay
AU - Kolonel, Laurence N.
AU - Kooperberg, Charles
AU - Krogh, Vittorio
AU - Kurtz, Robert C.
AU - Lacroix, Andrea
AU - Landgren, Annelie
AU - Landi, Maria Teresa
AU - Li, Donghui
AU - Liao, Linda M.
AU - Malats, Nuria
AU - McGlynn, Katherine A.
AU - McNeill, Lorna H.
AU - McWilliams, Robert R.
AU - Melin, Beatrice S.
AU - Mirabello, Lisa
AU - Peplonska, Beata
AU - Peters, Ulrike
AU - Petersen, Gloria M.
AU - Prokunina-Olsson, Ludmila
AU - Purdue, Mark
AU - Qiao, You Lin
AU - Rabe, Kari G.
AU - Rajaraman, Preetha
AU - Real, Francisco X.
AU - Riboli, Elio
AU - Rodríguez-Santiago, Benjamín
AU - Rothman, Nathaniel
AU - Ruder, Avima M.
AU - Savage, Sharon A.
AU - Schwartz, Ann G.
AU - Schwartz, Kendra L.
AU - Sesso, Howard D.
AU - Severi, Gianluca
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 - Viswanathan, Kala
AU - Wacholder, Sholom
AU - Wang, Zhaoming
AU - Weinstein, Stephanie J.
AU - Wheeler, William
AU - White, Emily
AU - Wiencke, John K.
AU - Wolpin, Brian M.
AU - Wu, Xifeng
AU - Wunder, Jay S.
AU - Yu, Kai
AU - Zanetti, Krista A.
AU - Zeleniuch-Jacquotte, Anne
AU - Ziegler, Regina G.
AU - De Andrade, Mariza
AU - Barnes, Kathleen C.
AU - Beaty, Terri H.
AU - Bierut, Laura J.
AU - Desch, Karl C.
AU - Doheny, Kimberly F.
AU - Feenstra, Bjarke
AU - Ginsburg, David
AU - Heit, John A.
AU - Kang, Jae H.
AU - Laurie, Cecilia A.
AU - Li, Jun Z.
AU - Lowe, William L.
AU - Marazita, Mary L.
AU - Melbye, Mads
AU - Mirel, Daniel B.
AU - Murray, Jeffrey C.
AU - Nelson, Sarah C.
AU - Pasquale, Louis R.
AU - Rice, Kenneth
AU - Wiggs, Janey L.
AU - Wise, Anastasia
AU - Tucker, Margaret
AU - Pérez-Jurado, Luis A.
AU - Laurie, Cathy C.
AU - Caporaso, Neil E.
AU - Yeager, Meredith
AU - Chanock, Stephen J.
PY - 2015/3/5
Y1 - 2015/3/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924140975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924140975&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2015.01.011
DO - 10.1016/j.ajhg.2015.01.011
M3 - Article
C2 - 25748358
AN - SCOPUS:84924140975
VL - 96
SP - 487
EP - 497
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -