Identification of SNP Targeted Pathways From Genome-wide Association Study (GWAS) Data

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Burcu Bakir-Gungor^1-3,*, Osman Ugur Sezerman³

KEGG ID	KEGG Term	Rank	Term Pvalue Corrected Bonferroni	Pathway Associated Genes Found in Subnetworks	Pathway Associated Genes Not Found in Subnetworks
KEGG:04512	ECM-receptor interaction	1	8,76E-21	COL4A2;  COL4A1;  ITGA2;  ITGB3;  ITGA4;  ITGB1;  SDC2;  COL5A1;  SDC3;  VWF;  LAMA3;  CD36*;  ITGA6;  CD44;  LAMA5;  ITGB8;  TNR;  ITGB6;  COL1A1*;  FN1;	GP9; HMMR; HSPG2; IBSP; ITGA1; ITGA10; ITGA11; ITGA2B; ITGA3; ITGA5; ITGA7; ITGA8; ITGA9; ITGAV; ITGB4; ITGB5; ITGB7; LAMA1; LAMA2; LAMA4; LAMB1; LAMB2; LAMB3; LAMB4; …
KEGG:04630	Jak-STAT signaling pathway	2	1,01E-19	PIK3CG;  IL6*;  IL2RB;  OSMR;  IL6ST*;  STAM2;  SOCS1;  CBL;  LIFR;  IL6R*;  STAT1;  STAT3;  IL11*;  IFNAR1;  TYK2*;  OSM*;  IFNAR2;  CBLB;  JAK1*;  CSF3R;  CSF2RB;  JAK2;  IL5RA;	CREBBP; CRLF2; CSF2; CSF2RA; CSF3; CSH1; CTF1; EP300; EPO; EPOR; GH1; GH2; GHR; GRB2; IFNA1; IFNA10; IFNA13; IFNA14; IFNA16; IFNA17; IFNA2; IFNA21; IFNA4; IFNA5; IFNA6; IFNA7; IFNA8; TPO; TSLP; …………………..
KEGG:04610	Complement and coagulation cascades	3	2,42E-19	PLAT;  KNG1;  F11;  MBL2;  F12*;  F10*;  C3;  F13A1;  PLG*;  PROC*;  VWF;  FGG*;  FGA*;  FGB*;  KLKB1;  F2*;  SERPINC1;  PROS1;  PLAU*;	A2M; BDKRB1; BDKRB2; C1QA; C1QB; C1QC; C1R; C1S; C2; C3AR1; C4A; C4B; C4BPA; C4BPB; C5; CD59; CFB; CFD; CFH; CFI; CPB2; CR1; CR2; F13B; SERPINA1; SERPINA5; SERPIND1; SERPINE1; ….
KEGG:04510	Focal adhesion	4	5,46E-19	TNC*;  ERBB2*;  BCAR1;  ITGB5;  ITGB3;  ITGB1;  PTK2*;  ITGB8;  PAK4;  ITGAV*;  ITGB6;  PAK1;  SPP1*;  FN1;  PRKCA;  EGFR;  FLT4;  ITGA2;  ITGA4;  PPP1CB;  FLNB;  VWF;  VEGFC;  ITGA9;  ITGA6;  ITGA5*;  FYN;  GSK3B;	PIP5K1C; PPP1CA; PPP1CC; PPP1R12A; PRKCB; PRKCG; PTEN; PXN; RAC1; RAC2; RAC3; RAF1; RHOA; ROCK1; ROCK2; SHC1; SHC2; SHC3; SHC4; SOS1; SOS2; SRC; THBS1; THBS2; THBS3; THBS4; TLN1; TLN2; TNN; TNR; TNXB; VASP; VAV1; VAV2; VAV3; VCL; VEGFA; VEGFB; VTN; XIAP; ZYX; …….
KEGG:04144	Endocytosis	5	1,14E-18	STAM2;  KIT;  CLTC;  IGF1R;  CDC42;  AP2B1;  SH3GLB1;  WWP1;  NEDD4L;  ITCH;  SH3GL3;  EGFR;  RET;  FLT1;  CBL;  HLA-C;  EPS15*;  CBLB;  AP2A2*;  NEDD4*;  NTRK1;  SH3GL2;  EPN1*;  DNM1*;  EPN2;	SMAD2; SMAD3; SMAD6; SMAD7; SMAP1; SMAP2; SMURF1; SMURF2; SNF8; SRC; STAM; STAMBP; TFRC; TGFB1; TGFB2; TGFB3; TGFBR1; TGFBR2; VPS45; VPS4A; VPS4B; VTA1; ZFYVE16; ZFYVE20; ZFYVE9; …………….

Table 2 | Pathway based representation of PANOGA results, focusing on subnetwork genes. The top 5 SNP targeted KEGG pathways are shown along with their KEGG term IDs, ranks and p-values in the 1st, 3rd and 4th columns, respectively. Pathway associated genes that are found in the subnetworks are shown in the 5th column. While the genes without ‘*’ symbol are SNP targeted genes (e.g. JAK2 gene in the Jak-STAT signaling pathway), the genes with ‘*’ symbol are identified in the subnetwork due to the neighbour effect (e.g. JAK1 gene in the Jak-STAT signaling pathway). The genes with neighbour effect (not targeted by SNPs) are incorporated using PPI network in the subnetwork identification step of PANOGA and they help to identify SNP targeted pathways, which can not be picked up using SNP targeted genes only. Column 6 displays other members (genes) of the identified SNP targeted pathway, that are not found in PANOGA subnetworks. Due to space constraints, a part of column 6 is shown here.