Table 1.
Selected positive GxE interactions obervered in human cases of schizophrenia
| Genetic variant | Environmental Factor | Outcomes | Reference |
|---|---|---|---|
| MHC(rs1051788) | Infection | Positive association between MHC SNP and seropositivity for CMV and HSV-1. SNP also associated with reduced PFC volume in SCZ patients |
Shirts, 2007 Prasad, 2010 |
| IL18R | Infection | Positive association between IL-18r SNP and seropositivity for HSV-1/2, and CMV in SCZ patients | Shirts, 2008b |
| CTNNA3(rs7902091) | Infection | Association between SCZ exposure and genotype only found in combination with CMV exposure | Borglum, 2014 |
| GRIN | Maternal infection | Maternal HSV-2 exposure linked to GRIN2B genetic variation, encoding for NMDAR subunits | Demontis, 2011 |
| HLA-DR1 | Season of birth | Association between winter birth and HLA-DR1 genotype in SCZ patients | Narita, 2000 |
| HLA-A24, A26 | Season of birth | No association observed between genotype and season of birth | Tochigi, 2002 |
| DRD4 | Season of birth | Risk association between psychosis and polymorphisms were dependent on season of birth | Chotain, 2003 |
| MTHFR(rs1801133) | Season of birth | No association between season of birth and genotype observed | Muntjewerff, 2011 |
| Residential Status | |||
| Established family history of disease | Urban living | Significant contribution to risk of developing psychosis seen in proband patients with family history of disease and living in an urban setting. | van Os, 2003; 2004 |
| Childhood Trauma | |||
| NOSAP1 | Childhood abuse | No observed additive effect of risk haplotype and abuse | Husted, 2010 |
| BDNF(Val66Met) | Childhood abuse | Met carriers show positive interaction between abuse and genetics | Alemany, 2011 |
| FOXP2(rs1456031) | Childhood abuse | Significant positive interaction between genotype and abuse, in predicting AVH in patients | McCarthy- Jones, 2014 |
| Established family history of disease | Childhood abuse | No significant association between abuse, family history and the development of psychotic disorders, in individuals reporting abuse | Fisher, 2014 |
| Stress | |||
| COMT, BDNF, 5- HTTLPR | Chronic stress | Additive interaction between genotype and stress on reduced hippocampal volume in human subjects | Rab, 2014 |
| COMT | Stress | COMT Val allele conveys a higher risk of psychotic outcome under stress | Stefanis, 2007 Simons, 2009 |
| COMT | Stress | COMT Met homozygous patients show more psychotic symptoms under stress | van Winkel, 2008 Collip, 2011 |
| COMT, MTHFR | Stress | Reactions to stress influenced by COMT genotype may be moderated by MTHFR genotype | Peerblooms, 2012 |
| NRG1(rs6994992) | Stress | NRG-1 genotype influences likelihood of unusual thoughts in conflict conditions | Keri, 2009 |
| Substance Abuse | |||
| COMT | Cannabis | COMT Val carriers show higher likelihood to develop psychosis after adolescent cannabis use |
Caspi, 2005 Henquet, 2006 van Winkel, 2011 |
| COMT | Cannabis | Negative findings to the above association |
Costas, 2011 Zammit, 2007 Kantrowitz, 2009 |
| AKT1(rs2494732) | Cannabis | Positive and dose dependent association between genotype, cannabis consumption and the development of psychosis |
van Winkel, 2011a,b Di Forti, 2012 |
| CBD1(rs12720071) | Cannabis | Positive association between cannabis use, CBD1 genotype and white matter volume in SCZ patients | Ho, 2011 |
| Established family history of disease | Cannabis | Significant association between cannabis use, family history of disease, and brain region volume | Malchow, 2013 |
| NRG1 | Cannabis | NRG1 genotype and cannabis administration have an additive effect on electrophysiology results reminiscent of schizophrenia | Stadelmann, 2010 |
| Various, including DRD2, DRD4, COMT, DAT | Methamphetami ne | Numerous significant associations have been found between meth use, psychotic symptoms and subject genotype | See section 3.3.2 |
| Obstetric Complications | |||
| Established family history of disease | Obstetric complications | Additive effect of family history and OC on CSF volume | Connon, 2002 |
| SCZ patient status | Neonatal hypoxia | Patients who had experienced hypoxia showed reduced hippocampal volume | Van Erp, 2002 |
| AKT1, BDNF, DTNBP1, GRM3 | Obstetric complications | Linkage found between serious obstetric complications, risk of SCZ and mutations in several hypoxia related genes | Nicodemus, 2008 |
| ARVCG, FADS2 | Pre-term birth | Genotype influenced white matter abnormalities in pre- term infants | Boardman, 2014 |
| GRM3 | Fetal hypoxia | Severe fetal hypoxia associated with smaller hippocampal volume in SCZ patients, correlated to GRM3 genotype | Haukvik, 2010 |