Whole genome sequence analysis of blood lipid levels in >66,000 individuals

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

Standard

Whole genome sequence analysis of blood lipid levels in >66,000 individuals. / Selvaraj, Margaret Sunitha; Li, Xihao; Li, Zilin; Pampana, Akhil; Zhang, David Y.; Park, Joseph; Aslibekyan, Stella; Bis, Joshua C.; Brody, Jennifer A.; Cade, Brian E.; Chuang, Lee Ming; Chung, Ren Hua; Curran, Joanne E.; de las Fuentes, Lisa; de Vries, Paul S.; Duggirala, Ravindranath; Freedman, Barry I.; Graff, Mariaelisa; Guo, Xiuqing; Heard-Costa, Nancy; Hidalgo, Bertha; Hwu, Chii Min; Irvin, Marguerite R.; Kelly, Tanika N.; Kral, Brian G.; Lange, Leslie; Li, Xiaohui; Lisa, Martin; Lubitz, Steven A.; Manichaikul, Ani W.; Michael, Preuss; Montasser, May E.; Morrison, Alanna C.; Naseri, Take; O’Connell, Jeffrey R.; Palmer, Nicholette D.; Peyser, Patricia A.; Reupena, Muagututia S.; Smith, Jennifer A.; Sun, Xiao; Taylor, Kent D.; Tracy, Russell P.; Tsai, Michael Y.; Wang, Zhe; Wang, Yuxuan; Loos, Ruth; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.

In: Nature Communications, Vol. 13, 5995, 2022.

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

Harvard

Selvaraj, MS, Li, X, Li, Z, Pampana, A, Zhang, DY, Park, J, Aslibekyan, S, Bis, JC, Brody, JA, Cade, BE, Chuang, LM, Chung, RH, Curran, JE, de las Fuentes, L, de Vries, PS, Duggirala, R, Freedman, BI, Graff, M, Guo, X, Heard-Costa, N, Hidalgo, B, Hwu, CM, Irvin, MR, Kelly, TN, Kral, BG, Lange, L, Li, X, Lisa, M, Lubitz, SA, Manichaikul, AW, Michael, P, Montasser, ME, Morrison, AC, Naseri, T, O’Connell, JR, Palmer, ND, Peyser, PA, Reupena, MS, Smith, JA, Sun, X, Taylor, KD, Tracy, RP, Tsai, MY, Wang, Z, Wang, Y, Loos, R & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium 2022, 'Whole genome sequence analysis of blood lipid levels in >66,000 individuals', Nature Communications, vol. 13, 5995. https://doi.org/10.1038/s41467-022-33510-7

APA

Selvaraj, M. S., Li, X., Li, Z., Pampana, A., Zhang, D. Y., Park, J., Aslibekyan, S., Bis, J. C., Brody, J. A., Cade, B. E., Chuang, L. M., Chung, R. H., Curran, J. E., de las Fuentes, L., de Vries, P. S., Duggirala, R., Freedman, B. I., Graff, M., Guo, X., ... NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium (2022). Whole genome sequence analysis of blood lipid levels in >66,000 individuals. Nature Communications, 13, [5995]. https://doi.org/10.1038/s41467-022-33510-7

Vancouver

Selvaraj MS, Li X, Li Z, Pampana A, Zhang DY, Park J et al. Whole genome sequence analysis of blood lipid levels in >66,000 individuals. Nature Communications. 2022;13. 5995. https://doi.org/10.1038/s41467-022-33510-7

Author

Selvaraj, Margaret Sunitha ; Li, Xihao ; Li, Zilin ; Pampana, Akhil ; Zhang, David Y. ; Park, Joseph ; Aslibekyan, Stella ; Bis, Joshua C. ; Brody, Jennifer A. ; Cade, Brian E. ; Chuang, Lee Ming ; Chung, Ren Hua ; Curran, Joanne E. ; de las Fuentes, Lisa ; de Vries, Paul S. ; Duggirala, Ravindranath ; Freedman, Barry I. ; Graff, Mariaelisa ; Guo, Xiuqing ; Heard-Costa, Nancy ; Hidalgo, Bertha ; Hwu, Chii Min ; Irvin, Marguerite R. ; Kelly, Tanika N. ; Kral, Brian G. ; Lange, Leslie ; Li, Xiaohui ; Lisa, Martin ; Lubitz, Steven A. ; Manichaikul, Ani W. ; Michael, Preuss ; Montasser, May E. ; Morrison, Alanna C. ; Naseri, Take ; O’Connell, Jeffrey R. ; Palmer, Nicholette D. ; Peyser, Patricia A. ; Reupena, Muagututia S. ; Smith, Jennifer A. ; Sun, Xiao ; Taylor, Kent D. ; Tracy, Russell P. ; Tsai, Michael Y. ; Wang, Zhe ; Wang, Yuxuan ; Loos, Ruth ; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. / Whole genome sequence analysis of blood lipid levels in >66,000 individuals. In: Nature Communications. 2022 ; Vol. 13.

Bibtex

@article{b9efa3a87c9940c28b25def71ba2b728,
title = "Whole genome sequence analysis of blood lipid levels in >66,000 individuals",
abstract = "Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.",
author = "Selvaraj, {Margaret Sunitha} and Xihao Li and Zilin Li and Akhil Pampana and Zhang, {David Y.} and Joseph Park and Stella Aslibekyan and Bis, {Joshua C.} and Brody, {Jennifer A.} and Cade, {Brian E.} and Chuang, {Lee Ming} and Chung, {Ren Hua} and Curran, {Joanne E.} and {de las Fuentes}, Lisa and {de Vries}, {Paul S.} and Ravindranath Duggirala and Freedman, {Barry I.} and Mariaelisa Graff and Xiuqing Guo and Nancy Heard-Costa and Bertha Hidalgo and Hwu, {Chii Min} and Irvin, {Marguerite R.} and Kelly, {Tanika N.} and Kral, {Brian G.} and Leslie Lange and Xiaohui Li and Martin Lisa and Lubitz, {Steven A.} and Manichaikul, {Ani W.} and Preuss Michael and Montasser, {May E.} and Morrison, {Alanna C.} and Take Naseri and O{\textquoteright}Connell, {Jeffrey R.} and Palmer, {Nicholette D.} and Peyser, {Patricia A.} and Reupena, {Muagututia S.} and Smith, {Jennifer A.} and Xiao Sun and Taylor, {Kent D.} and Tracy, {Russell P.} and Tsai, {Michael Y.} and Zhe Wang and Yuxuan Wang and Ruth Loos and {NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-33510-7",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Whole genome sequence analysis of blood lipid levels in >66,000 individuals

AU - Selvaraj, Margaret Sunitha

AU - Li, Xihao

AU - Li, Zilin

AU - Pampana, Akhil

AU - Zhang, David Y.

AU - Park, Joseph

AU - Aslibekyan, Stella

AU - Bis, Joshua C.

AU - Brody, Jennifer A.

AU - Cade, Brian E.

AU - Chuang, Lee Ming

AU - Chung, Ren Hua

AU - Curran, Joanne E.

AU - de las Fuentes, Lisa

AU - de Vries, Paul S.

AU - Duggirala, Ravindranath

AU - Freedman, Barry I.

AU - Graff, Mariaelisa

AU - Guo, Xiuqing

AU - Heard-Costa, Nancy

AU - Hidalgo, Bertha

AU - Hwu, Chii Min

AU - Irvin, Marguerite R.

AU - Kelly, Tanika N.

AU - Kral, Brian G.

AU - Lange, Leslie

AU - Li, Xiaohui

AU - Lisa, Martin

AU - Lubitz, Steven A.

AU - Manichaikul, Ani W.

AU - Michael, Preuss

AU - Montasser, May E.

AU - Morrison, Alanna C.

AU - Naseri, Take

AU - O’Connell, Jeffrey R.

AU - Palmer, Nicholette D.

AU - Peyser, Patricia A.

AU - Reupena, Muagututia S.

AU - Smith, Jennifer A.

AU - Sun, Xiao

AU - Taylor, Kent D.

AU - Tracy, Russell P.

AU - Tsai, Michael Y.

AU - Wang, Zhe

AU - Wang, Yuxuan

AU - Loos, Ruth

AU - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

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

PY - 2022

Y1 - 2022

N2 - Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

AB - Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

U2 - 10.1038/s41467-022-33510-7

DO - 10.1038/s41467-022-33510-7

M3 - Journal article

C2 - 36220816

AN - SCOPUS:85139608936

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5995

ER -

ID: 325024342