Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing
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Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing. / Jakubek, Yasminka A.; Zhou, Ying; Stilp, Adrienne; Bacon, Jason; Wong, Justin W.; Ozcan, Zuhal; Arnett, Donna; Barnes, Kathleen; Bis, Joshua C.; Boerwinkle, Eric; Brody, Jennifer A.; Carson, April P.; Chasman, Daniel I.; Chen, Jiawen; Cho, Michael; Conomos, Matthew P.; Cox, Nancy; Doyle, Margaret F.; Fornage, Myriam; Guo, Xiuqing; Kardia, Sharon L.R.; Lewis, Joshua P.; Loos, Ruth J.F.; Ma, Xiaolong; Machiela, Mitchell J.; Mack, Taralynn M.; Mathias, Rasika A.; Mitchell, Braxton D.; Mychaleckyj, Josyf C.; North, Kari; Pankratz, Nathan; Peyser, Patricia A.; Preuss, Michael H.; Psaty, Bruce; Raffield, Laura M.; Vasan, Ramachandran S.; Redline, Susan; Rich, Stephen S.; Rotter, Jerome I.; Silverman, Edwin K.; Smith, Jennifer A.; Smith, Aaron P.; Taub, Margaret; Taylor, Kent D.; Yun, Jeong; Li, Yun; Desai, Pinkal; Bick, Alexander G.; Reiner, Alexander P.; Scheet, Paul; Auer, Paul L.
In: Nature Genetics, Vol. 55, No. 11, 2023, p. 1912-1919.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing
AU - Jakubek, Yasminka A.
AU - Zhou, Ying
AU - Stilp, Adrienne
AU - Bacon, Jason
AU - Wong, Justin W.
AU - Ozcan, Zuhal
AU - Arnett, Donna
AU - Barnes, Kathleen
AU - Bis, Joshua C.
AU - Boerwinkle, Eric
AU - Brody, Jennifer A.
AU - Carson, April P.
AU - Chasman, Daniel I.
AU - Chen, Jiawen
AU - Cho, Michael
AU - Conomos, Matthew P.
AU - Cox, Nancy
AU - Doyle, Margaret F.
AU - Fornage, Myriam
AU - Guo, Xiuqing
AU - Kardia, Sharon L.R.
AU - Lewis, Joshua P.
AU - Loos, Ruth J.F.
AU - Ma, Xiaolong
AU - Machiela, Mitchell J.
AU - Mack, Taralynn M.
AU - Mathias, Rasika A.
AU - Mitchell, Braxton D.
AU - Mychaleckyj, Josyf C.
AU - North, Kari
AU - Pankratz, Nathan
AU - Peyser, Patricia A.
AU - Preuss, Michael H.
AU - Psaty, Bruce
AU - Raffield, Laura M.
AU - Vasan, Ramachandran S.
AU - Redline, Susan
AU - Rich, Stephen S.
AU - Rotter, Jerome I.
AU - Silverman, Edwin K.
AU - Smith, Jennifer A.
AU - Smith, Aaron P.
AU - Taub, Margaret
AU - Taylor, Kent D.
AU - Yun, Jeong
AU - Li, Yun
AU - Desai, Pinkal
AU - Bick, Alexander G.
AU - Reiner, Alexander P.
AU - Scheet, Paul
AU - Auer, Paul L.
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.
AB - Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.
U2 - 10.1038/s41588-023-01553-1
DO - 10.1038/s41588-023-01553-1
M3 - Journal article
C2 - 37904051
AN - SCOPUS:85175190300
VL - 55
SP - 1912
EP - 1919
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -
ID: 373511920