Ancestral diversity in lipoprotein(a) studies helps address evidence gaps

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

Standard

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps. / Lee, Moa P.; Dimos, Sofia F.; Raffield, Laura M.; Wang, Zhe; Ballou, Anna F.; Downie, Carolina G.; Arehart, Christopher H.; Correa, Adolfo; De Vries, Paul S.; Du, Zhaohui; Gignoux, Christopher R.; Gordon-Larsen, Penny; Guo, Xiuqing; Haessler, Jeffrey; Howard, Annie Green; Hu, Yao; Kassahun, Helina; Kent, Shia T.; Lopez, J. Antonio G.; Monda, Keri L.; North, Kari E.; Peters, Ulrike; Preuss, Michael H.; Rich, Stephen S.; Rhodes, Shannon L.; Yao, Jie; Yarosh, Rina; Tsai, Michael Y.; Rotter, Jerome I.; Kooperberg, Charles L.; Loos, Ruth J.F.; Ballantyne, Christie; Avery, Christy L.; Graff, Mariaelisa.

In: Open Heart, Vol. 10, No. 2, e002382, 2023.

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

Harvard

Lee, MP, Dimos, SF, Raffield, LM, Wang, Z, Ballou, AF, Downie, CG, Arehart, CH, Correa, A, De Vries, PS, Du, Z, Gignoux, CR, Gordon-Larsen, P, Guo, X, Haessler, J, Howard, AG, Hu, Y, Kassahun, H, Kent, ST, Lopez, JAG, Monda, KL, North, KE, Peters, U, Preuss, MH, Rich, SS, Rhodes, SL, Yao, J, Yarosh, R, Tsai, MY, Rotter, JI, Kooperberg, CL, Loos, RJF, Ballantyne, C, Avery, CL & Graff, M 2023, 'Ancestral diversity in lipoprotein(a) studies helps address evidence gaps', Open Heart, vol. 10, no. 2, e002382. https://doi.org/10.1136/openhrt-2023-002382

APA

Lee, M. P., Dimos, S. F., Raffield, L. M., Wang, Z., Ballou, A. F., Downie, C. G., Arehart, C. H., Correa, A., De Vries, P. S., Du, Z., Gignoux, C. R., Gordon-Larsen, P., Guo, X., Haessler, J., Howard, A. G., Hu, Y., Kassahun, H., Kent, S. T., Lopez, J. A. G., ... Graff, M. (2023). Ancestral diversity in lipoprotein(a) studies helps address evidence gaps. Open Heart, 10(2), [e002382]. https://doi.org/10.1136/openhrt-2023-002382

Vancouver

Lee MP, Dimos SF, Raffield LM, Wang Z, Ballou AF, Downie CG et al. Ancestral diversity in lipoprotein(a) studies helps address evidence gaps. Open Heart. 2023;10(2). e002382. https://doi.org/10.1136/openhrt-2023-002382

Author

Lee, Moa P. ; Dimos, Sofia F. ; Raffield, Laura M. ; Wang, Zhe ; Ballou, Anna F. ; Downie, Carolina G. ; Arehart, Christopher H. ; Correa, Adolfo ; De Vries, Paul S. ; Du, Zhaohui ; Gignoux, Christopher R. ; Gordon-Larsen, Penny ; Guo, Xiuqing ; Haessler, Jeffrey ; Howard, Annie Green ; Hu, Yao ; Kassahun, Helina ; Kent, Shia T. ; Lopez, J. Antonio G. ; Monda, Keri L. ; North, Kari E. ; Peters, Ulrike ; Preuss, Michael H. ; Rich, Stephen S. ; Rhodes, Shannon L. ; Yao, Jie ; Yarosh, Rina ; Tsai, Michael Y. ; Rotter, Jerome I. ; Kooperberg, Charles L. ; Loos, Ruth J.F. ; Ballantyne, Christie ; Avery, Christy L. ; Graff, Mariaelisa. / Ancestral diversity in lipoprotein(a) studies helps address evidence gaps. In: Open Heart. 2023 ; Vol. 10, No. 2.

Bibtex

@article{fba17165aed94ae2877bd4563fca8b91,
title = "Ancestral diversity in lipoprotein(a) studies helps address evidence gaps",
abstract = "Introduction The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. Methods Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. Results Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R 2 =15% in East Asians) to high (R 2 =50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10 -6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. Conclusions Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps. ",
keywords = "biomarkers, epidemiology, genetic association studies, genome-wide association study",
author = "Lee, {Moa P.} and Dimos, {Sofia F.} and Raffield, {Laura M.} and Zhe Wang and Ballou, {Anna F.} and Downie, {Carolina G.} and Arehart, {Christopher H.} and Adolfo Correa and {De Vries}, {Paul S.} and Zhaohui Du and Gignoux, {Christopher R.} and Penny Gordon-Larsen and Xiuqing Guo and Jeffrey Haessler and Howard, {Annie Green} and Yao Hu and Helina Kassahun and Kent, {Shia T.} and Lopez, {J. Antonio G.} and Monda, {Keri L.} and North, {Kari E.} and Ulrike Peters and Preuss, {Michael H.} and Rich, {Stephen S.} and Rhodes, {Shannon L.} and Jie Yao and Rina Yarosh and Tsai, {Michael Y.} and Rotter, {Jerome I.} and Kooperberg, {Charles L.} and Loos, {Ruth J.F.} and Christie Ballantyne and Avery, {Christy L.} and Mariaelisa Graff",
note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2023",
doi = "10.1136/openhrt-2023-002382",
language = "English",
volume = "10",
journal = "Open Heart",
issn = "2398-595X",
publisher = "BMJ",
number = "2",

}

RIS

TY - JOUR

T1 - Ancestral diversity in lipoprotein(a) studies helps address evidence gaps

AU - Lee, Moa P.

AU - Dimos, Sofia F.

AU - Raffield, Laura M.

AU - Wang, Zhe

AU - Ballou, Anna F.

AU - Downie, Carolina G.

AU - Arehart, Christopher H.

AU - Correa, Adolfo

AU - De Vries, Paul S.

AU - Du, Zhaohui

AU - Gignoux, Christopher R.

AU - Gordon-Larsen, Penny

AU - Guo, Xiuqing

AU - Haessler, Jeffrey

AU - Howard, Annie Green

AU - Hu, Yao

AU - Kassahun, Helina

AU - Kent, Shia T.

AU - Lopez, J. Antonio G.

AU - Monda, Keri L.

AU - North, Kari E.

AU - Peters, Ulrike

AU - Preuss, Michael H.

AU - Rich, Stephen S.

AU - Rhodes, Shannon L.

AU - Yao, Jie

AU - Yarosh, Rina

AU - Tsai, Michael Y.

AU - Rotter, Jerome I.

AU - Kooperberg, Charles L.

AU - Loos, Ruth J.F.

AU - Ballantyne, Christie

AU - Avery, Christy L.

AU - Graff, Mariaelisa

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2023

Y1 - 2023

N2 - Introduction The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. Methods Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. Results Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R 2 =15% in East Asians) to high (R 2 =50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10 -6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. Conclusions Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.

AB - Introduction The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations. Methods Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. Results Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R 2 =15% in East Asians) to high (R 2 =50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10 -6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects. Conclusions Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.

KW - biomarkers

KW - epidemiology

KW - genetic association studies

KW - genome-wide association study

U2 - 10.1136/openhrt-2023-002382

DO - 10.1136/openhrt-2023-002382

M3 - Journal article

C2 - 37648373

AN - SCOPUS:85170665617

VL - 10

JO - Open Heart

JF - Open Heart

SN - 2398-595X

IS - 2

M1 - e002382

ER -

ID: 367907621