Overlap of genetic influences in phenotypes classically categorized as psychiatric vs medical disorders

Table 1 Gene2MeSH results

Gene symbol	Entrez gene ID	MeSH descriptor	MeSH qualifier	PubMed citations	Citations expected	Fold change	χ2	P value
AKT1	207	Schizophrenia	Genetics	26	8.97	2.9	31.4	2.97E-06
		Breast Neoplasms	Pathology	91	36.40	2.5	78.2	1.63E-14
COMT	1312	Schizophrenia	Genetics	176	6.96	25.3	4107.4	5.06E-186
		Breast Neoplasms	Genetics	68	28.33	2.4	55.3	8.43E-11
CYP2D6	1565	Schizophrenia	Drug therapy	45	4.89	9.2	330.0	1.28E-28
		Breast Neoplasms	Drug therapy	42	20.00	2.1	24.5	9.59E-06
ERBB4	2066	Schizophrenia	Genetics	6	0.59	10.1	90.4	1.63E-08
		Breast Neoplasms	Pathology	27	4.43	6.1	114.9	5.28E-14
NRG1	3084	Schizophrenia	Genetics	98	1.85	53.1	5011.8	2.84E-140
		Breast Neoplasms	Pathology	24	7.50	3.2	36.1	7.39E-07
SOD2	6648	Schizophrenia	Genetics	16	3.64	4.4	42.8	1.07E-06
		Breast Neoplasms	Genetics	50	14.71	3.4	85.1	9.33E-14

The intersection of Gene2MeSH output for MeSH “descriptor: Schizophrenia” and MeSH “descriptor: Breast neoplasms” yields 6 genes significantly over-represented in PubMed abstracts annotated for both descriptors. Fold changes are calculated within Gene2MeSH as citations observed/expected. χ² statistics and their corresponding P-values are also developed from these values. This gene set became input to the GeneGo modeling.

Table 2 Over-represented disease annotation for systems biology model

Disease	Percent of network genes annotated (%)	P value
Ovarian neoplasms	76.74	5.80E-29
Ovarian diseases	76.74	3.24E-27
Adnexal diseases	76.74	3.89E-27
Mesothelioma	48.84	2.04E-26
Neoplasms, mesothelial	48.84	2.50E-26
Gonadal disorders	76.74	4.23E-26
Genital neoplasms, female	79.07	8.70E-26
Hyperoxia	30.23	2.10E-23
Genital diseases, female	83.72	4.75E-22
Astrocytoma	72.09	4.82E-22
Neoplasms, connective and soft tissue	62.79	1.64E-21
Glioblastoma	69.77	3.67E-21

The 43 genes in the GeneGo model developed from the 6 candidate genes show significant over-representation for cancers, especially hormone sensitive cancers, and brain diseases, including brain cancers. P values characterizing the significance of enrichment are calculated within the GeneGo software based on a hypergeometric distribution.