@article{Castaneda:2022:hmg/ddab236,
author = {Castaneda, AB and Petty, LE and Scholz, M and Jansen, R and Weiss, S and Zhang, X and Schramm, K and Beutner, F and Kirsten, H and Schminke, U and Hwang, S-J and Marzi, C and Dhana, K and Seldenrijk, A and Krohn, K and Homuth, G and Wolf, P and Peters, MJ and Dörr, M and Peters, A and van, Meurs JBJ and Uitterlinden, AG and Kavousi, M and Levy, D and Herder, C and van, Grootheest G and Waldenberger, M and Meisinger, C and Rathmann, W and Thiery, J and Polak, J and Koenig, W and Seissler, J and Bis, JC and Franceshini, N and Giambartolomei, C and Cohorts, for Heart and Aging Research in Genomic Epidemiology CHARGE Subclinical Working Group and Hofman, A and Franco, OH and Penninx, BWJH and Prokisch, H and Völzke, H and Loeffler, M and O'Donnell, CJ and Below, JE and Dehghan, A and de, Vries PS},
doi = {hmg/ddab236},
journal = {Hum Mol Genet},
pages = {1171--1182},
title = {Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.},
url = {http://dx.doi.org/10.1093/hmg/ddab236},
volume = {31},
year = {2022}
}

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TY  - JOUR
AB  - Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.
AU  - Castaneda,AB
AU  - Petty,LE
AU  - Scholz,M
AU  - Jansen,R
AU  - Weiss,S
AU  - Zhang,X
AU  - Schramm,K
AU  - Beutner,F
AU  - Kirsten,H
AU  - Schminke,U
AU  - Hwang,S-J
AU  - Marzi,C
AU  - Dhana,K
AU  - Seldenrijk,A
AU  - Krohn,K
AU  - Homuth,G
AU  - Wolf,P
AU  - Peters,MJ
AU  - Dörr,M
AU  - Peters,A
AU  - van,Meurs JBJ
AU  - Uitterlinden,AG
AU  - Kavousi,M
AU  - Levy,D
AU  - Herder,C
AU  - van,Grootheest G
AU  - Waldenberger,M
AU  - Meisinger,C
AU  - Rathmann,W
AU  - Thiery,J
AU  - Polak,J
AU  - Koenig,W
AU  - Seissler,J
AU  - Bis,JC
AU  - Franceshini,N
AU  - Giambartolomei,C
AU  - Cohorts,for Heart and Aging Research in Genomic Epidemiology CHARGE Subclinical Working Group
AU  - Hofman,A
AU  - Franco,OH
AU  - Penninx,BWJH
AU  - Prokisch,H
AU  - Völzke,H
AU  - Loeffler,M
AU  - O'Donnell,CJ
AU  - Below,JE
AU  - Dehghan,A
AU  - de,Vries PS
DO  - hmg/ddab236
EP  - 1182
PY  - 2022///
SP  - 1171
TI  - Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.
T2  - Hum Mol Genet
UR  - http://dx.doi.org/10.1093/hmg/ddab236
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34788810
VL  - 31
ER  - 

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