%0 Journal Article %1 Pott2020-nn %A Pott, Janne %A Beutner, Frank %A Horn, Katrin %A Kirsten, Holger %A Olischer, Kay %A Wirkner, Kerstin %A Loeffler, Markus %A Scholz, Markus %D 2020 %I Public Library of Science (PLoS) %J PLoS One %K %N 5 %P e0233728 %T Genome-wide analysis of carotid plaque burden suggests a role of IL5 in men %V 15 %X BACKGROUND: Carotid artery plaque is an established marker of subclinical atherosclerosis with pronounced sex-dimorphism. Here, we aimed to identify genetic variants associated with carotid plaque burden (CPB) and to examine potential sex-specific genetic effects on plaque sizes. METHODS AND RESULTS: We defined six operationalizations of CPB considering plaques in common carotid arteries, carotid bulb, and internal carotid arteries. We performed sex-specific genome-wide association analyses for all traits in the LIFE-Adult cohort (n = 727 men and n = 550 women) and tested significantly associated loci for sex-specific effects. In order to identify causal genes, we analyzed candidate gene expression data for correlation with CPB traits and corresponding sex-specific effects. Further, we tested if previously reported SNP associations with CAD and plaque prevalence are also associated with CBP. We found seven loci with suggestive significance for CPB (p<3.33x10-7), explaining together between 6 and 13\% of the CPB variance. Sex-specific analysis showed a genome-wide significant hit for men at 5q31.1 (rs201629990, $\beta$ = -0.401, p = 5.22x10-9), which was not associated in women ($\beta$ = -0.127, p = 0.093) with a significant difference in effect size (p = 0.008). Analyses of gene expression data suggested IL5 as the most plausible candidate, as it reflected the same sex-specific association with CPBs (p = 0.037). Known plaque prevalence or CAD loci showed no enrichment in the association with CPB. CONCLUSIONS: We showed that CPB is a complementary trait in analyzing genetics of subclinical atherosclerosis. We detected a novel locus for plaque size in men only suggesting a role of IL5. Several estrogen response elements in this locus point towards a functional explanation of the observed sex-specific effect.

@article{Pott2020-nn, abstract = {BACKGROUND: Carotid artery plaque is an established marker of subclinical atherosclerosis with pronounced sex-dimorphism. Here, we aimed to identify genetic variants associated with carotid plaque burden (CPB) and to examine potential sex-specific genetic effects on plaque sizes. METHODS AND RESULTS: We defined six operationalizations of CPB considering plaques in common carotid arteries, carotid bulb, and internal carotid arteries. We performed sex-specific genome-wide association analyses for all traits in the LIFE-Adult cohort (n = 727 men and n = 550 women) and tested significantly associated loci for sex-specific effects. In order to identify causal genes, we analyzed candidate gene expression data for correlation with CPB traits and corresponding sex-specific effects. Further, we tested if previously reported SNP associations with CAD and plaque prevalence are also associated with CBP. We found seven loci with suggestive significance for CPB (p<3.33x10-7), explaining together between 6 and 13\% of the CPB variance. Sex-specific analysis showed a genome-wide significant hit for men at 5q31.1 (rs201629990, $\beta$ = -0.401, p = 5.22x10-9), which was not associated in women ($\beta$ = -0.127, p = 0.093) with a significant difference in effect size (p = 0.008). Analyses of gene expression data suggested IL5 as the most plausible candidate, as it reflected the same sex-specific association with CPBs (p = 0.037). Known plaque prevalence or CAD loci showed no enrichment in the association with CPB. CONCLUSIONS: We showed that CPB is a complementary trait in analyzing genetics of subclinical atherosclerosis. We detected a novel locus for plaque size in men only suggesting a role of IL5. Several estrogen response elements in this locus point towards a functional explanation of the observed sex-specific effect.}, added-at = {2024-09-10T11:56:37.000+0200}, author = {Pott, Janne and Beutner, Frank and Horn, Katrin and Kirsten, Holger and Olischer, Kay and Wirkner, Kerstin and Loeffler, Markus and Scholz, Markus}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/278cdf4293d3154fd71fa4350df9cb126/scadsfct}, copyright = {http://creativecommons.org/licenses/by/4.0/}, interhash = {f3f3b7dbbede853d8a1fba3e63854d16}, intrahash = {78cdf4293d3154fd71fa4350df9cb126}, journal = {PLoS One}, keywords = {}, language = {en}, month = may, number = 5, pages = {e0233728}, publisher = {Public Library of Science (PLoS)}, timestamp = {2024-09-10T15:15:57.000+0200}, title = {Genome-wide analysis of carotid plaque burden suggests a role of {IL5} in men}, volume = 15, year = 2020 }