Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program

Research output: Contribution to journal › Journal article › Research › peer-review

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Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program. / Wheeler, Marsha M.; Stilp, Adrienne M.; Rao, Shuquan; Halldórsson, Bjarni V.; Beyter, Doruk; Wen, Jia; Mihkaylova, Anna V.; McHugh, Caitlin P.; Lane, John; Jiang, Min Zhi; Raffield, Laura M.; Jun, Goo; Sedlazeck, Fritz J.; Metcalf, Ginger; Yao, Yao; Bis, Joshua B.; Chami, Nathalie; de Vries, Paul S.; Desai, Pinkal; Floyd, James S.; Gao, Yan; Kammers, Kai; Kim, Wonji; Moon, Jee Young; Ratan, Aakrosh; Yanek, Lisa R.; Almasy, Laura; Becker, Lewis C.; Blangero, John; Cho, Michael H.; Curran, Joanne E.; Fornage, Myriam; Kaplan, Robert C.; Lewis, Joshua P.; Loos, Ruth J.F.; Mitchell, Braxton D.; Morrison, Alanna C.; Preuss, Michael; Psaty, Bruce M.; Rich, Stephen S.; Rotter, Jerome I.; Tang, Hua; Tracy, Russell P.; Boerwinkle, Eric; Abecasis, Goncalo R.; Blackwell, Thomas W.; Smith, Albert V.; Johnson, Andrew D.; Mathias, Rasika A.; Nickerson, Deborah A.; Conomos, Matthew P.; Li, Yun; Þorsteinsdóttir, Unnur; Magnússon, Magnús K.; Stefansson, Kari; Pankratz, Nathan D.; Bauer, Daniel E.; Auer, Paul L.; Reiner, Alex P.

In: Nature Communications, Vol. 13, 7592, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wheeler, MM, Stilp, AM, Rao, S, Halldórsson, BV, Beyter, D, Wen, J, Mihkaylova, AV, McHugh, CP, Lane, J, Jiang, MZ, Raffield, LM, Jun, G, Sedlazeck, FJ, Metcalf, G, Yao, Y, Bis, JB, Chami, N, de Vries, PS, Desai, P, Floyd, JS, Gao, Y, Kammers, K, Kim, W, Moon, JY, Ratan, A, Yanek, LR, Almasy, L, Becker, LC, Blangero, J, Cho, MH, Curran, JE, Fornage, M, Kaplan, RC, Lewis, JP, Loos, RJF, Mitchell, BD, Morrison, AC, Preuss, M, Psaty, BM, Rich, SS, Rotter, JI, Tang, H, Tracy, RP, Boerwinkle, E, Abecasis, GR, Blackwell, TW, Smith, AV, Johnson, AD, Mathias, RA, Nickerson, DA, Conomos, MP, Li, Y, Þorsteinsdóttir, U, Magnússon, MK, Stefansson, K, Pankratz, ND, Bauer, DE, Auer, PL & Reiner, AP 2022, 'Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program', Nature Communications, vol. 13, 7592. https://doi.org/10.1038/s41467-022-35354-7

APA

Wheeler, M. M., Stilp, A. M., Rao, S., Halldórsson, B. V., Beyter, D., Wen, J., Mihkaylova, A. V., McHugh, C. P., Lane, J., Jiang, M. Z., Raffield, L. M., Jun, G., Sedlazeck, F. J., Metcalf, G., Yao, Y., Bis, J. B., Chami, N., de Vries, P. S., Desai, P., ... Reiner, A. P. (2022). Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program. Nature Communications, 13, [7592]. https://doi.org/10.1038/s41467-022-35354-7

Vancouver

Wheeler MM, Stilp AM, Rao S, Halldórsson BV, Beyter D, Wen J et al. Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program. Nature Communications. 2022;13. 7592. https://doi.org/10.1038/s41467-022-35354-7

Author

Wheeler, Marsha M. ; Stilp, Adrienne M. ; Rao, Shuquan ; Halldórsson, Bjarni V. ; Beyter, Doruk ; Wen, Jia ; Mihkaylova, Anna V. ; McHugh, Caitlin P. ; Lane, John ; Jiang, Min Zhi ; Raffield, Laura M. ; Jun, Goo ; Sedlazeck, Fritz J. ; Metcalf, Ginger ; Yao, Yao ; Bis, Joshua B. ; Chami, Nathalie ; de Vries, Paul S. ; Desai, Pinkal ; Floyd, James S. ; Gao, Yan ; Kammers, Kai ; Kim, Wonji ; Moon, Jee Young ; Ratan, Aakrosh ; Yanek, Lisa R. ; Almasy, Laura ; Becker, Lewis C. ; Blangero, John ; Cho, Michael H. ; Curran, Joanne E. ; Fornage, Myriam ; Kaplan, Robert C. ; Lewis, Joshua P. ; Loos, Ruth J.F. ; Mitchell, Braxton D. ; Morrison, Alanna C. ; Preuss, Michael ; Psaty, Bruce M. ; Rich, Stephen S. ; Rotter, Jerome I. ; Tang, Hua ; Tracy, Russell P. ; Boerwinkle, Eric ; Abecasis, Goncalo R. ; Blackwell, Thomas W. ; Smith, Albert V. ; Johnson, Andrew D. ; Mathias, Rasika A. ; Nickerson, Deborah A. ; Conomos, Matthew P. ; Li, Yun ; Þorsteinsdóttir, Unnur ; Magnússon, Magnús K. ; Stefansson, Kari ; Pankratz, Nathan D. ; Bauer, Daniel E. ; Auer, Paul L. ; Reiner, Alex P. / Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program. In: Nature Communications. 2022 ; Vol. 13.

Bibtex

@article{ee74c099ebbc4d638840bafcb5b8b16f,
title = "Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program",
abstract = "Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression.",
author = "Wheeler, {Marsha M.} and Stilp, {Adrienne M.} and Shuquan Rao and Halld{\'o}rsson, {Bjarni V.} and Doruk Beyter and Jia Wen and Mihkaylova, {Anna V.} and McHugh, {Caitlin P.} and John Lane and Jiang, {Min Zhi} and Raffield, {Laura M.} and Goo Jun and Sedlazeck, {Fritz J.} and Ginger Metcalf and Yao Yao and Bis, {Joshua B.} and Nathalie Chami and {de Vries}, {Paul S.} and Pinkal Desai and Floyd, {James S.} and Yan Gao and Kai Kammers and Wonji Kim and Moon, {Jee Young} and Aakrosh Ratan and Yanek, {Lisa R.} and Laura Almasy and Becker, {Lewis C.} and John Blangero and Cho, {Michael H.} and Curran, {Joanne E.} and Myriam Fornage and Kaplan, {Robert C.} and Lewis, {Joshua P.} and Loos, {Ruth J.F.} and Mitchell, {Braxton D.} and Morrison, {Alanna C.} and Michael Preuss and Psaty, {Bruce M.} and Rich, {Stephen S.} and Rotter, {Jerome I.} and Hua Tang and Tracy, {Russell P.} and Eric Boerwinkle and Abecasis, {Goncalo R.} and Blackwell, {Thomas W.} and Smith, {Albert V.} and Johnson, {Andrew D.} and Mathias, {Rasika A.} and Nickerson, {Deborah A.} and Conomos, {Matthew P.} and Yun Li and Unnur {\TH}orsteinsd{\'o}ttir and Magn{\'u}sson, {Magn{\'u}s K.} and Kari Stefansson and Pankratz, {Nathan D.} and Bauer, {Daniel E.} and Auer, {Paul L.} and Reiner, {Alex P.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-35354-7",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program

AU - Wheeler, Marsha M.

AU - Stilp, Adrienne M.

AU - Rao, Shuquan

AU - Halldórsson, Bjarni V.

AU - Beyter, Doruk

AU - Wen, Jia

AU - Mihkaylova, Anna V.

AU - McHugh, Caitlin P.

AU - Lane, John

AU - Jiang, Min Zhi

AU - Raffield, Laura M.

AU - Jun, Goo

AU - Sedlazeck, Fritz J.

AU - Metcalf, Ginger

AU - Yao, Yao

AU - Bis, Joshua B.

AU - Chami, Nathalie

AU - de Vries, Paul S.

AU - Desai, Pinkal

AU - Floyd, James S.

AU - Gao, Yan

AU - Kammers, Kai

AU - Kim, Wonji

AU - Moon, Jee Young

AU - Ratan, Aakrosh

AU - Yanek, Lisa R.

AU - Almasy, Laura

AU - Becker, Lewis C.

AU - Blangero, John

AU - Cho, Michael H.

AU - Curran, Joanne E.

AU - Fornage, Myriam

AU - Kaplan, Robert C.

AU - Lewis, Joshua P.

AU - Loos, Ruth J.F.

AU - Mitchell, Braxton D.

AU - Morrison, Alanna C.

AU - Preuss, Michael

AU - Psaty, Bruce M.

AU - Rich, Stephen S.

AU - Rotter, Jerome I.

AU - Tang, Hua

AU - Tracy, Russell P.

AU - Boerwinkle, Eric

AU - Abecasis, Goncalo R.

AU - Blackwell, Thomas W.

AU - Smith, Albert V.

AU - Johnson, Andrew D.

AU - Mathias, Rasika A.

AU - Nickerson, Deborah A.

AU - Conomos, Matthew P.

AU - Li, Yun

AU - Þorsteinsdóttir, Unnur

AU - Magnússon, Magnús K.

AU - Stefansson, Kari

AU - Pankratz, Nathan D.

AU - Bauer, Daniel E.

AU - Auer, Paul L.

AU - Reiner, Alex P.

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression.

AB - Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression.

U2 - 10.1038/s41467-022-35354-7

DO - 10.1038/s41467-022-35354-7

M3 - Journal article

C2 - 36481753

AN - SCOPUS:85143558600

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7592

ER -

ID: 329746234