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

H Grallert; J Dupuis; JC Bis; Abbas Dehghan; M Barbalic; J Baumert; C Lu; NL Smith; André Uitterlinden; R Roberts; N Khuseyinova; RB Schnabel; KM Rice; Fernando Rivadeneira; RC Hoogeveen; JD Fontes; C Meisinger; JF Keaney; R Lemaitre; YS Aulchenko; RS Vasan; S Ellis; SL Hazen; Cornelia Duijn; JJ Nelson; W Marz; H Schunkert; RM McPherson; HA Stirnadel-Farrant; BM Psaty; C Gieger; D Siscovick; Bert Hofman; T Illig; M Cushman; JF Yamamoto; JI Rotter; MG Larson; AFR Stewart; E Boerwinkle; JCM Witteman; RP Tracy; W Koenig; EJ Benjamin; CM Ballantyne

doi:10.1093/eurheartj/ehr372

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

H Grallert
, J Dupuis
, JC Bis
, Abbas Dehghan
, M Barbalic
, J Baumert
, C Lu
, NL Smith
, André Uitterlinden
, R Roberts
, N Khuseyinova
, RB Schnabel
, KM Rice
, Fernando Rivadeneira
, RC Hoogeveen
, JD Fontes
, C Meisinger
, JF Keaney
, R Lemaitre
, YS Aulchenko

RS Vasan, S Ellis, SL Hazen, Cornelia Duijn, JJ Nelson, W Marz, H Schunkert, RM McPherson, HA Stirnadel-Farrant, BM Psaty, C Gieger, D Siscovick, Bert Hofman, T Illig, M Cushman, JF Yamamoto, JI Rotter, MG Larson, AFR Stewart, E Boerwinkle, JCM Witteman, RP Tracy, W Koenig, EJ Benjamin, CM Ballantyne

External organisation

Research output: Contribution to journal › Article › Academic › peer-review

84 Citations (Scopus)

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 x 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 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.

Original language	Undefined/Unknown
Pages (from-to)	238-251
Number of pages	14
Journal	European Heart Journal
Volume	33
Issue number	2
DOIs	https://doi.org/10.1093/eurheartj/ehr372
Publication status	Published - 2012

Research programs

EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

Access to Document

10.1093/eurheartj/ehr372

http://hdl.handle.net/1765/70187

Cite this

Grallert, H., Dupuis, J., Bis, JC., Dehghan, A., Barbalic, M., Baumert, J., Lu, C., Smith, NL., Uitterlinden, A., Roberts, R., Khuseyinova, N., Schnabel, RB., Rice, KM., Rivadeneira, F., Hoogeveen, RC., Fontes, JD., Meisinger, C., Keaney, JF., Lemaitre, R., ... 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. European Heart Journal, 33(2), 238-251. https://doi.org/10.1093/eurheartj/ehr372

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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 x 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 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.",

author = "H Grallert and J Dupuis and JC Bis and Abbas Dehghan and M Barbalic and J Baumert and C Lu and NL Smith and Andr{\'e} Uitterlinden and R Roberts and N Khuseyinova and RB Schnabel and KM Rice and Fernando Rivadeneira and RC Hoogeveen and JD Fontes and C Meisinger and JF Keaney and R Lemaitre and YS Aulchenko and RS Vasan and S Ellis and SL Hazen and Cornelia Duijn and JJ Nelson and W Marz and H Schunkert and RM McPherson and HA Stirnadel-Farrant and BM Psaty and C Gieger and D Siscovick and Bert Hofman and T Illig and M Cushman and JF Yamamoto and JI Rotter and MG Larson and AFR Stewart and E Boerwinkle and JCM Witteman and RP Tracy and W Koenig and EJ Benjamin and CM Ballantyne",

year = "2012",

doi = "10.1093/eurheartj/ehr372",

language = "Undefined/Unknown",

volume = "33",

pages = "238--251",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

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Grallert, H, Dupuis, J, Bis, JC, Dehghan, A, Barbalic, M, Baumert, J, Lu, C, Smith, NL, Uitterlinden, A, 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, Duijn, C, Nelson, JJ, Marz, W, Schunkert, H, McPherson, RM, Stirnadel-Farrant, HA, Psaty, BM, Gieger, C, Siscovick, D, Hofman, B, 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', European Heart Journal, vol. 33, no. 2, pp. 238-251. https://doi.org/10.1093/eurheartj/ehr372

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, H; Dupuis, J; Bis, JC et al.
In: European Heart Journal, Vol. 33, No. 2, 2012, p. 238-251.

Research output: Contribution to journal › Article › Academic › peer-review

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, H

AU - Dupuis, J

AU - Bis, JC

AU - Dehghan, Abbas

AU - Barbalic, M

AU - Baumert, J

AU - Lu, C

AU - Smith, NL

AU - Uitterlinden, André

AU - Roberts, R

AU - Khuseyinova, N

AU - Schnabel, RB

AU - Rice, KM

AU - Rivadeneira, Fernando

AU - Hoogeveen, RC

AU - Fontes, JD

AU - Meisinger, C

AU - Keaney, JF

AU - Lemaitre, R

AU - Aulchenko, YS

AU - Vasan, RS

AU - Ellis, S

AU - Hazen, SL

AU - Duijn, Cornelia

AU - Nelson, JJ

AU - Marz, W

AU - Schunkert, H

AU - McPherson, RM

AU - Stirnadel-Farrant, HA

AU - Psaty, BM

AU - Gieger, C

AU - Siscovick, D

AU - Hofman, Bert

AU - Illig, T

AU - Cushman, M

AU - Yamamoto, JF

AU - Rotter, JI

AU - Larson, MG

AU - Stewart, AFR

AU - Boerwinkle, E

AU - Witteman, JCM

AU - Tracy, RP

AU - Koenig, W

AU - Benjamin, EJ

AU - Ballantyne, CM

PY - 2012

Y1 - 2012

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 x 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 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 x 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 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.

U2 - 10.1093/eurheartj/ehr372

DO - 10.1093/eurheartj/ehr372

M3 - Article

C2 - 22003152

SN - 0195-668X

VL - 33

SP - 238

EP - 251

JO - European Heart Journal

JF - European Heart Journal

IS - 2

ER -