Division of Biostatistics, University of Minnesota

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Division of Biostatistics, University of Minnesota Integrating eQTL data with GWAS summary statistics identifies novel genes and pathways associated with schizophrenia Chong Wu and Wei Pan Division of Biostatistics, University of Minnesota Oct. 17, 2017

PrediXcan copyright @ Gusev et. al. (2016)

Novel reformulation PrediXcan = TWAS = (weighted) Sum test; Sum test will lose statistical power under many situations; More powerful tests, such as SSU and aSPU, can be applied.

Pathway-based analysis

Gene-based analysis results Table: The numbers of the significant genes identified by analyzing the SCZ data. The numbers a/b in each cell indicate the numbers of (a) the significant genes; (b) the significant genes covering at least one genome-wide significant SNP within 500 kb in the SCZ data. YFS NTR METSIM CMC Combined TWAS 63/46 49/39 4332 69/50 202/142 SSU 127/94 78/59 108/76 124/85 381/255 aSPU 105/83 69/60 87/72 110/82 314/235

Pathway-based analysis results Table: The significant and novel gene sets containing no significant genes as identified by a new pathway-based method. ID Description P-value GO:1902710 GABA receptor complex 0.0E+00 GO:1901661 quinone metabolic process 2.0E-08 GO:0016339 calcium-dependent cell-cell adhesion 2.2E-07 GO:0030315 T-tubule 2.3E-07 GO:0007528 neuromuscular junction development 5.7E-07 GO:0003143 embryonic heart tube morphogenesis 9.5E-07 GO:0007569 cell aging 1.6E-06 GO:0035050 embryonic heart tube development 1.8E-06

Summary We have developed a powerful adaptive test (aSPU) to integrate GWAS and eQTL data; PrediXcan and TWAS, can be regarded as a special case of our proposed test; Extend TWAS from gene-based analysis to pathway-based analysis can identify new pathways that may be missed by gene-based analysis Chong Wu (a biostatistics Ph.D. candidate at the University of Minnesota, chongwu@umn.edu) is looking for an Assistant Professor or Research Scientist position.