SNPs associated with circulating chemerin levels at genome-wide significant levels.

<p>Inflation factor of all single studies were negligible (maximum λ = 1.014 in the Sorbs cohort). No inflation of meta-analysis results was observed (λ = 0.99). Positions of SNPs are given according to HapMap2 CEU, Release 24, dbSNP-build 126, NCBI 36 as the reference panel. Effect directions are given for the coding allele. <i>ß</i> Beta coefficient of regression model.</p><p>Chr: chromosome; <i>β</i>: beta; SE: standard error; <i>LRRC61</i>: leucine rich repeat containing 61; <i>ACTR3C</i>: ARP3 actin-related protein 3 homolog C; <i>RARRES2</i>: retionic acid receptor responder 2; <i>REPIN1</i>: replication initiator 1; <i>ZBED6CL</i>: ZBED6 C-terminal like.</p><p>SNPs associated with circulating chemerin levels at genome-wide significant levels.</p

Regional association plot for the top-hit of association with chemerin levels on chromosome 7.

<p>Regional association plot for the top-hit of association with chemerin levels on chromosome 7.</p

eQTL analysis for rs7806429 in PBMCs of the Sorbs cohort.

<p>eQTL analysis for rs7806429 in PBMCs of the Sorbs cohort.</p

Association of rs7806429 with <i>RARRES2</i> expression in subcutaneous and visceral adipose tissue.

<p>Linear regression analyses adjusted for age and BMI (and sex for the total cohort). Subjects with T2D were not included in the analyses.</p><p>SC: subcutaneous; VIS: visceral; β: beta.</p><p>Association of rs7806429 with <i>RARRES2</i> expression in subcutaneous and visceral adipose tissue.</p

Correlation of serum chemerin concentrations with anthropometric parameters and markers of glucose metabolism, serum lipids and renal function in the Sorbs cohort.

<p>Associations were assessed in a linear regression model adjusting for age, sex and BMI (except for analysis of BMI itself). HOMA-IR was calculated as published by Matthews et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004854#pgen.1004854-Matthews1" target="_blank">[35]</a>. The Stumvoll Index refers to Stumvoll ISI_{(0 and 120 min) and} Stumvoll ISI_{(0 and 30 min)}<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004854#pgen.1004854-Stumvoll1" target="_blank">[36]</a>. Glomerular filtration rate (GFR) was calculated using the MDRD formula. <i>ß</i> Beta coefficient of linear regression model.</p><p>Correlation of serum chemerin concentrations with anthropometric parameters and markers of glucose metabolism, serum lipids and renal function in the Sorbs cohort.</p

Significant canonical pathways in the KOFA F4 discovery panel.

<p>Significant canonical pathways in the KOFA F4 discovery panel.</p

Significant associations between CRP and DNA methylation sites in the discovery and validation panels.

<p>Significant associations between CRP and DNA methylation sites in the discovery and validation panels.</p

Manhattan Plot of the results of the genome-wide DNA methylation analysis on CRP conducted in the KORA F4 discovery sample.

<p>The Manhattan plot displays all analyzed CpG sites with their calculated p-values. Threshold of epigenome-wide significance: P = 1.13E-07.</p

a–d): eQTLs with simultaneous impact on expression levels of at least five genes in <i>trans</i>.

<p>a) Chromosome 12. The eQTL was located upstream of <i>lysozyme</i> (<i>LYZ</i>), a gene residing on chromosome <i>12q15</i>. It is associated with expression levels of the seven transcripts <i>cAMP responsive element binding protein 1 (CREB1), SHC SH2-domain binding protein 1 (SHCBP1), arylformamidase (AFMID), KIAA0101, ITPK1 antisense RNA 1 (ITPK1-AS1), EP300 interacting inhibitor of differentiation 2B (EID2B)</i>, and <i>CDKN2A interacting protein N-terminal like (CDKN2AIPNL)</i>. b) Chromosome 11. The eQTL was found intronic of the <i>hemoglobin beta</i> (<i>HBB</i>) gene on chromosome <i>11p15.4</i> and was associated with the regulation of 13 genes distributed across the genome in <i>trans</i>: <i>PWP1 homolog (PWP1), phosphatidylserine synthase 1 (PTDSS1), CCHC-type zinc finger, nucleic acid binding protein (CNBP), trafficking protein particle complex 11 (TRAPPC11), histone deacetylase 1 (HDAC1), WD repeat domain 59 (WDR59), G protein pathway suppressor 1 (GPS1), ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1), aarF domain containing kinase 2 (ADCK2), deoxythymidylate kinase (thymidylate kinase) (DTYMK), WD repeat domain 37 (WDR37), spectrin repeat containing, nuclear envelope 2 (SYNE2)</i>, and <i>RAD51 paralog C (RAD51C)</i>. c) Chromosome 3. The eQTL on chromosome 3 was located intronic of the <i>rho guanin nucleotid exchange factor 3 (ARHGEF3)</i> gene at <i>3p14.3</i>. We observed a significant impact on the regulation of twelve genes, <i>integrin beta 5 (ITGB5), platelet glycoprotein IX (GP9), carboxy-terminal domain, RNA polymerase II, polypeptide A small phosphatase-like (CTDSPL), protein S alpha (PROS1), guanylate cyclase soluble subunit alpha-3 (GUCY1A3)</i>, <i>caldesmon 1 (CALD1)</i>, <i>tetraspanin 9 (TSPAN9), arachidonate 12-lipoxygenase (ALOX12), parvin beta (PARVB), N-acetyltransferase 8B (NAT8B), multimerin 1 (MMRN1)</i>, and <i>C-type lectin domain family 1, member B (CLEC1B)</i>. d) Chromosome 2. The eQTL upstream of <i>atonal homolog 8 (ATOH8)</i> residing on chromosome 2p11.2 exerts simultaneous impact on expression levels of six genes: <i>paroxysmal nonkinesigenic dyskinesia (PNKD)</i> and <i>calcium homeostasis modulator 1 (CALHM1)</i>, <i>zink finger protein 93 (ZNF93), dynein, light chain, roadblock-type 2 (DYNLRB2), growth hormone-releasing hormone receptor (GHRHR)</i>, and <i>MutL-homolog 3(MLH3)</i>.</p

Baseline characteristics of study participants.

<p>Baseline characteristics of study participants.</p