@article {Kjaergaard831, author = {Alisa D Kjaergaard and Julia S Johansen and B{\o}rge G Nordestgaard and Stig E Bojesen}, title = {Genetic variants in CHI3L1 influencing YKL-40 levels: resequencing 900 individuals and genotyping 9000 individuals from the general population}, volume = {50}, number = {12}, pages = {831--837}, year = {2013}, doi = {10.1136/jmedgenet-2013-101908}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population. Methods We resequenced the promoter, all 10 exons and exon-flanking intron segments of CHI3L1 in 904 individuals from the Danish general population (n=8899) with extreme plasma YKL-40 levels, adjusted for age. To potentially identify clinically important genetic variants with elevated plasma YKL-40 levels, we included twice as many individuals with the highest plasma YKL-40 levels (n=603) compared with the lowest plasma YKL-40 levels (n=301). Next, we mapped linkage disequilibrium for all variants with a minor allele frequency (MAF)\>0.005. Finally, all participants were genotyped for eight variants that had divergent MAFs in the two extreme plasma YKL-40 groups. Results We identified 59 genetic variants in CHI3L1. Fifteen of the genetic variants were associated with plasma YKL-40 levels. Three promoter SNPs, 1 non-synonymous SNP, and four intronic SNPs in CHI3L1 were associated with plasma YKL-40 levels at or below genome-wide association significance levels (unadjusted p for trend: from 4 {\texttimes} 10-8 to 6 {\texttimes} 10-243; age adjusted percentiles p for trend: from 3 {\texttimes} 10-12~to 2 {\texttimes} 10-304). Conclusions In a systematic search to identify genetic variants influencing plasma YKL-40 levels, we identified eight SNPs associated with plasma YKL-40 levels in the general population.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/50/12/831}, eprint = {https://jmg.bmj.com/content/50/12/831.full.pdf}, journal = {Journal of Medical Genetics} }