Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration

M Abdullah Said; Ming Wai Yeung; Yordi J van de Vegte; Jan Walter Benjamins; Robin P F Dullaart; Sanni Ruotsalainen; Samuli Ripatti; Pradeep Natarajan; Luis Eduardo Juarez-Orozco; Niek Verweij; P van der Harst

doi:10.1161/ATVBAHA.120.315300

Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration

M Abdullah Said, Ming Wai Yeung, Yordi J van de Vegte, Jan Walter Benjamins, Robin P F Dullaart, Sanni Ruotsalainen, Samuli Ripatti, Pradeep Natarajan, Luis Eduardo Juarez-Orozco, Niek Verweij^*, P van der Harst^*

^*Corresponding author voor dit werk

Cardiovasculair Centrum

Onderzoeksoutput › Academic › peer review

24 Citaten (Scopus)

110 Downloads (Pure)

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Objective:

Lipoprotein(a) (Lp[a]) is associated with coronary artery disease (CAD) but also to LDL (low-density lipoprotein) cholesterol. The genetic architecture of Lp(a) remains incompletely understood, as well as its independence of LDL cholesterol in its association to CAD. We investigated the genetic determinants of Lp(a) concentrations in a large prospective multiethnic cohort. We tested the association for potential causality between genetically determined higher Lp(a) concentrations and CAD using a multivariable Mendelian randomization strategy.

Approach and Results:

We studied 371 212 participants of the UK Biobank with available Lp(a) and genome-wide genetic data. Genome-wide association analyses confirmed 2 known and identified 37 novel loci (P

Conclusions:

This study supports an LDL cholesterol-independent causal link between Lp(a) and CAD. A rare missense variant in the LPA gene locus appears to be protective in people with the Lp(a) increasing variant of rs10455872. In the search for therapeutic targets of Lp(a), future work should focus on understanding the functional consequences of this missense variant.

Originele taal-2	English
Pagina's (van-tot)	1792-1780
Aantal pagina's	9
Tijdschrift	Arteriosclerosis, thrombosis, and vascular biology
Volume	41
Nummer van het tijdschrift	5
Vroegere onlinedatum	2021
DOI's	https://doi.org/10.1161/ATVBAHA.120.315300
Status	Published - 5-mei-2021

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Genome wide association study and identification of a protective missense variant on lipoprotein(a) concentration - GWAS summary statistics data files
Said, A. (Contributor), Mendeley Data, 2-mrt.-2021
DOI: 10.17632/r5snpvg5ty.1, https://data.mendeley.com/datasets/r5snpvg5ty
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Said, M. A., Yeung, M. W., van de Vegte, Y. J., Benjamins, J. W., Dullaart, R. P. F., Ruotsalainen, S., Ripatti, S., Natarajan, P., Juarez-Orozco, L. E., Verweij, N., & van der Harst, P. (2021). Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration. Arteriosclerosis, thrombosis, and vascular biology, 41(5), 1792-1780. https://doi.org/10.1161/ATVBAHA.120.315300

Said, M Abdullah ; Yeung, Ming Wai ; van de Vegte, Yordi J et al. / Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report : Protective Missense Variant on Lipoprotein(a) Concentration. In: Arteriosclerosis, thrombosis, and vascular biology. 2021 ; Vol. 41, Nr. 5. blz. 1792-1780.

@article{bd7d5a939fd64f1e9fb6858c7ce5445b,

title = "Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration",

abstract = "Objective:Lipoprotein(a) (Lp[a]) is associated with coronary artery disease (CAD) but also to LDL (low-density lipoprotein) cholesterol. The genetic architecture of Lp(a) remains incompletely understood, as well as its independence of LDL cholesterol in its association to CAD. We investigated the genetic determinants of Lp(a) concentrations in a large prospective multiethnic cohort. We tested the association for potential causality between genetically determined higher Lp(a) concentrations and CAD using a multivariable Mendelian randomization strategy.Approach and Results:We studied 371 212 participants of the UK Biobank with available Lp(a) and genome-wide genetic data. Genome-wide association analyses confirmed 2 known and identified 37 novel loci (PConclusions:This study supports an LDL cholesterol-independent causal link between Lp(a) and CAD. A rare missense variant in the LPA gene locus appears to be protective in people with the Lp(a) increasing variant of rs10455872. In the search for therapeutic targets of Lp(a), future work should focus on understanding the functional consequences of this missense variant.",

keywords = "causality, coronary artery disease, genetics, lipoproteins, polymorphism, single nucleotide, GENETIC-VARIANTS, METAANALYSIS, RISK",

author = "Said, {M Abdullah} and Yeung, {Ming Wai} and {van de Vegte}, {Yordi J} and Benjamins, {Jan Walter} and Dullaart, {Robin P F} and Sanni Ruotsalainen and Samuli Ripatti and Pradeep Natarajan and Juarez-Orozco, {Luis Eduardo} and Niek Verweij and {van der Harst}, P",

year = "2021",

month = may,

day = "5",

doi = "10.1161/ATVBAHA.120.315300",

language = "English",

volume = "41",

pages = "1792--1780",

journal = "Arteriosclerosis, thrombosis, and vascular biology",

issn = "1079-5642",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "5",

}

Said, MA , Yeung, MW , van de Vegte, YJ , Benjamins, JW , Dullaart, RPF, Ruotsalainen, S, Ripatti, S, Natarajan, P, Juarez-Orozco, LE, Verweij, N & van der Harst, P 2021, 'Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration', Arteriosclerosis, thrombosis, and vascular biology, vol. 41, nr. 5, blz. 1792-1780. https://doi.org/10.1161/ATVBAHA.120.315300

Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration. / Said, M Abdullah ; Yeung, Ming Wai ; van de Vegte, Yordi J et al.
In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 41, Nr. 5, 05.05.2021, blz. 1792-1780.

Onderzoeksoutput › Academic › peer review

TY - JOUR

T1 - Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report

T2 - Protective Missense Variant on Lipoprotein(a) Concentration

AU - Said, M Abdullah

AU - Yeung, Ming Wai

AU - van de Vegte, Yordi J

AU - Benjamins, Jan Walter

AU - Dullaart, Robin P F

AU - Ruotsalainen, Sanni

AU - Ripatti, Samuli

AU - Natarajan, Pradeep

AU - Juarez-Orozco, Luis Eduardo

AU - Verweij, Niek

AU - van der Harst, P

PY - 2021/5/5

Y1 - 2021/5/5

N2 - Objective:Lipoprotein(a) (Lp[a]) is associated with coronary artery disease (CAD) but also to LDL (low-density lipoprotein) cholesterol. The genetic architecture of Lp(a) remains incompletely understood, as well as its independence of LDL cholesterol in its association to CAD. We investigated the genetic determinants of Lp(a) concentrations in a large prospective multiethnic cohort. We tested the association for potential causality between genetically determined higher Lp(a) concentrations and CAD using a multivariable Mendelian randomization strategy.Approach and Results:We studied 371 212 participants of the UK Biobank with available Lp(a) and genome-wide genetic data. Genome-wide association analyses confirmed 2 known and identified 37 novel loci (PConclusions:This study supports an LDL cholesterol-independent causal link between Lp(a) and CAD. A rare missense variant in the LPA gene locus appears to be protective in people with the Lp(a) increasing variant of rs10455872. In the search for therapeutic targets of Lp(a), future work should focus on understanding the functional consequences of this missense variant.

AB - Objective:Lipoprotein(a) (Lp[a]) is associated with coronary artery disease (CAD) but also to LDL (low-density lipoprotein) cholesterol. The genetic architecture of Lp(a) remains incompletely understood, as well as its independence of LDL cholesterol in its association to CAD. We investigated the genetic determinants of Lp(a) concentrations in a large prospective multiethnic cohort. We tested the association for potential causality between genetically determined higher Lp(a) concentrations and CAD using a multivariable Mendelian randomization strategy.Approach and Results:We studied 371 212 participants of the UK Biobank with available Lp(a) and genome-wide genetic data. Genome-wide association analyses confirmed 2 known and identified 37 novel loci (PConclusions:This study supports an LDL cholesterol-independent causal link between Lp(a) and CAD. A rare missense variant in the LPA gene locus appears to be protective in people with the Lp(a) increasing variant of rs10455872. In the search for therapeutic targets of Lp(a), future work should focus on understanding the functional consequences of this missense variant.

KW - causality

KW - coronary artery disease

KW - genetics

KW - lipoproteins

KW - polymorphism

KW - single nucleotide

KW - GENETIC-VARIANTS

KW - METAANALYSIS

KW - RISK

U2 - 10.1161/ATVBAHA.120.315300

DO - 10.1161/ATVBAHA.120.315300

M3 - Article

C2 - 33730874

SN - 1079-5642

VL - 41

SP - 1792

EP - 1780

JO - Arteriosclerosis, thrombosis, and vascular biology

JF - Arteriosclerosis, thrombosis, and vascular biology

IS - 5

ER -

Said MA , Yeung MW , van de Vegte YJ , Benjamins JW , Dullaart RPF, Ruotsalainen S et al. Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration. Arteriosclerosis, thrombosis, and vascular biology. 2021 mei 5;41(5):1792-1780. Epub 2021. doi: 10.1161/ATVBAHA.120.315300

Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report: Protective Missense Variant on Lipoprotein(a) Concentration

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Genome wide association study and identification of a protective missense variant on lipoprotein(a) concentration - GWAS summary statistics data files

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