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Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies

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Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies. / Grallert, Harald; Dupuis, Josée; Bis, Joshua C; Dehghan, Abbas; Barbalic, Maja; Baumert, Jens; Lu, Chen; Smith, Nicholas L; Uitterlinden, André G; Roberts, Robert; Khuseyinova, Natalie; Schnabel, Renate B; Rice, Kenneth M; Rivadeneira, Fernando; Hoogeveen, Ron C; Fontes, João Daniel; Meisinger, Christa; Keaney, John F; Lemaitre, Rozenn; Aulchenko, Yurii S; Vasan, Ramachandran S; Ellis, Stephen; Hazen, Stanley L; van Duijn, Cornelia M; Nelson, Jeanenne J; März, Winfried; Schunkert, Heribert; McPherson, Ruth M; Stirnadel-Farrant, Heide A; Psaty, Bruce M; Gieger, Christian; Siscovick, David; Hofman, Albert; Illig, Thomas; Cushman, Mary; Yamamoto, Jennifer F; Rotter, Jerome I; Larson, Martin G; Stewart, Alexandre F R; Boerwinkle, Eric; Witteman, Jacqueline C M; Tracy, Russell P; Koenig, Wolfgang; Benjamin, Emelia J; Ballantyne, Christie M.

In: EUR HEART J, Vol. 33, No. 2, 01.2012, p. 238-251.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research

Harvard

Grallert, H, Dupuis, J, Bis, JC, Dehghan, A, Barbalic, M, Baumert, J, Lu, C, Smith, NL, Uitterlinden, AG, Roberts, R, Khuseyinova, N, Schnabel, RB, Rice, KM, Rivadeneira, F, Hoogeveen, RC, Fontes, JD, Meisinger, C, Keaney, JF, Lemaitre, R, Aulchenko, YS, Vasan, RS, Ellis, S, Hazen, SL, van Duijn, CM, Nelson, JJ, März, W, Schunkert, H, McPherson, RM, Stirnadel-Farrant, HA, Psaty, BM, Gieger, C, Siscovick, D, Hofman, A, Illig, T, Cushman, M, Yamamoto, JF, Rotter, JI, Larson, MG, Stewart, AFR, Boerwinkle, E, Witteman, JCM, Tracy, RP, Koenig, W, Benjamin, EJ & Ballantyne, CM 2012, 'Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies', EUR HEART J, vol. 33, no. 2, pp. 238-251. https://doi.org/10.1093/eurheartj/ehr372

APA

Grallert, H., Dupuis, J., Bis, J. C., Dehghan, A., Barbalic, M., Baumert, J., Lu, C., Smith, N. L., Uitterlinden, A. G., Roberts, R., Khuseyinova, N., Schnabel, R. B., Rice, K. M., Rivadeneira, F., Hoogeveen, R. C., Fontes, J. D., Meisinger, C., Keaney, J. F., Lemaitre, R., ... Ballantyne, C. M. (2012). Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies. EUR HEART J, 33(2), 238-251. https://doi.org/10.1093/eurheartj/ehr372

Vancouver

Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J et al. Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies. EUR HEART J. 2012 Jan;33(2):238-251. https://doi.org/10.1093/eurheartj/ehr372

Bibtex

@article{5b73fcca1203442ca47c6b222b83a214,
title = "Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies",
abstract = "AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study.CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.",
keywords = "1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Coronary Artery Disease/genetics, Coronary Disease/genetics, Female, Genetic Loci/genetics, Genome-Wide Association Study, Humans, Male, Middle Aged, Phospholipases A2/genetics, Polymorphism, Single Nucleotide/genetics",
author = "Harald Grallert and Jos{\'e}e Dupuis and Bis, {Joshua C} and Abbas Dehghan and Maja Barbalic and Jens Baumert and Chen Lu and Smith, {Nicholas L} and Uitterlinden, {Andr{\'e} G} and Robert Roberts and Natalie Khuseyinova and Schnabel, {Renate B} and Rice, {Kenneth M} and Fernando Rivadeneira and Hoogeveen, {Ron C} and Fontes, {Jo{\~a}o Daniel} and Christa Meisinger and Keaney, {John F} and Rozenn Lemaitre and Aulchenko, {Yurii S} and Vasan, {Ramachandran S} and Stephen Ellis and Hazen, {Stanley L} and {van Duijn}, {Cornelia M} and Nelson, {Jeanenne J} and Winfried M{\"a}rz and Heribert Schunkert and McPherson, {Ruth M} and Stirnadel-Farrant, {Heide A} and Psaty, {Bruce M} and Christian Gieger and David Siscovick and Albert Hofman and Thomas Illig and Mary Cushman and Yamamoto, {Jennifer F} and Rotter, {Jerome I} and Larson, {Martin G} and Stewart, {Alexandre F R} and Eric Boerwinkle and Witteman, {Jacqueline C M} and Tracy, {Russell P} and Wolfgang Koenig and Benjamin, {Emelia J} and Ballantyne, {Christie M}",
year = "2012",
month = jan,
doi = "10.1093/eurheartj/ehr372",
language = "English",
volume = "33",
pages = "238--251",
journal = "EUR HEART J",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies

AU - Grallert, Harald

AU - Dupuis, Josée

AU - Bis, Joshua C

AU - Dehghan, Abbas

AU - Barbalic, Maja

AU - Baumert, Jens

AU - Lu, Chen

AU - Smith, Nicholas L

AU - Uitterlinden, André G

AU - Roberts, Robert

AU - Khuseyinova, Natalie

AU - Schnabel, Renate B

AU - Rice, Kenneth M

AU - Rivadeneira, Fernando

AU - Hoogeveen, Ron C

AU - Fontes, João Daniel

AU - Meisinger, Christa

AU - Keaney, John F

AU - Lemaitre, Rozenn

AU - Aulchenko, Yurii S

AU - Vasan, Ramachandran S

AU - Ellis, Stephen

AU - Hazen, Stanley L

AU - van Duijn, Cornelia M

AU - Nelson, Jeanenne J

AU - März, Winfried

AU - Schunkert, Heribert

AU - McPherson, Ruth M

AU - Stirnadel-Farrant, Heide A

AU - Psaty, Bruce M

AU - Gieger, Christian

AU - Siscovick, David

AU - Hofman, Albert

AU - Illig, Thomas

AU - Cushman, Mary

AU - Yamamoto, Jennifer F

AU - Rotter, Jerome I

AU - Larson, Martin G

AU - Stewart, Alexandre F R

AU - Boerwinkle, Eric

AU - Witteman, Jacqueline C M

AU - Tracy, Russell P

AU - Koenig, Wolfgang

AU - Benjamin, Emelia J

AU - Ballantyne, Christie M

PY - 2012/1

Y1 - 2012/1

N2 - AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study.CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.

AB - AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study.CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.

KW - 1-Alkyl-2-acetylglycerophosphocholine Esterase

KW - Aged

KW - Coronary Artery Disease/genetics

KW - Coronary Disease/genetics

KW - Female

KW - Genetic Loci/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Phospholipases A2/genetics

KW - Polymorphism, Single Nucleotide/genetics

U2 - 10.1093/eurheartj/ehr372

DO - 10.1093/eurheartj/ehr372

M3 - SCORING: Journal article

C2 - 22003152

VL - 33

SP - 238

EP - 251

JO - EUR HEART J

JF - EUR HEART J

SN - 0195-668X

IS - 2

ER -