Study description of KORA F4, SHIP-TREND and EGCUT.

<p>Study description of KORA F4, SHIP-TREND and EGCUT.</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

Triangular relationships between eQTL-SNPs, gene expression levels in <i>trans</i> and phenotypic traits.

<p>Figure 4a: Adiponectin. ₁ Measured in the fasting state. ₂ Measured 2-hours after an oral glucose load in oral glucose tolerance test. Figure 4b: Mean Platelet Volume (MPV). The association between SNP and mean platelet volume was assessed in 4,159 KORA S4 participants, those between gene expression levels and mean platelet volume in 889 participants of the KORA F4 study. Figure 4c–e: Correlation analyses combining genetic, metabolomics and transcriptomics data in 712 participants of the KORA F4 study.</p

Results of the pathway analysis using Ingenuity Pathway Analysis.

<p>Results of the pathway analysis using Ingenuity Pathway Analysis.</p

Manhattan plot of all analyzed <i>cis-</i>eQTLs with their calculated p-values in the KORA F4 study.

<p>Manhattan plot of all analyzed <i>cis-</i>eQTLs with their calculated p-values in the KORA F4 study.</p

All <i>trans</i>-eQTLs with p-values below 2.81E-12 in the KORA F4 study.

<p>All <i>trans</i>-eQTLs with p-values below 2.81E-12 in the KORA F4 study.</p

Master regulatory sites – eQTL-SNPs with simultaneous impact on the expression of at least five genes.

<p>*only the SNP which displayed strongest associations in the region is displayed.</p