Table 1 1.
Common susceptibility genes in schizophrenia (SCZ) and type 2 diabetes mellitus (T2DM)
| Candidate genes | Location | Official full name | Functions | Method | Samples | References |
|---|---|---|---|---|---|---|
| Common cascade | ||||||
| ACE (Upstream of Akt/GSK3) | 17q23.3 | angiotensin I converting enzyme | Hydrolyze angiotensin I into angiotensin 2 | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| ARHGEF11 (Rho GTPase) | 1q23.1 | Rho guanine nucleotide exchange factor 11 | Numerous cellular process, synaptic plasticity | Association study | T2DM (n = 685) vs. Con (n = 461) | Böttcher et al. (2008) |
| Association study | SCZ (n = 490) vs. Con (n = 500) | Mizuki et al. (2014) | ||||
| BCL9 (Wnt/β-catenin) | 1q21.1 | B-cell CLL/lymphoma 9 | Wnt signaling pathway | Association study | SCZ (n = 4,187) vs. Con (n = 5,772) | Li et al. (2011) |
| CNV analysis | Cumulative scoring evidence,based on 32 CNV studies in SCZ | Luo et al. (2014) | ||||
| GWAS | T2DM (n = 402) vs. Con (n = 1,092) | Anderson et al. (2015) | ||||
| COMT (Upstream of Akt/GSK3) | 22q11.21 | catechol-O-methyltransferase | Degradation of catecholamines | CNV analysis | Cumulative scoring evidence,based on 32 CNV studies in SCZ | Luo et al. (2014) |
| Association study | T2DM (n = 595) vs. Con (n = 725) | Xiu et al. (2015) | ||||
| TCF7L2 (Wnt/β-catenin) | 10q25.2-3 | transcription factor 7 like 2 | Participates in the Wnt signaling pathway | Association study | T2DM (n = 2,201) | Lyssenko et al. (2008) |
| GWAS | SCZ (n = 924), T2D (n = 822), comorbid (n = 505); controls (n = 1,125) | Hackinger et al. (2018) | ||||
| Inflammation | ||||||
| ANXA1 | 9q21.13 | annexin A1 | Anti-inflammatory activity, endogenous regulator of RhoA | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| APOE | 19q13.32 | apolipoprotein E | Lipid homeostasis and inflammation | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| C4 | 6p21.33 | complement C4 | Encodes complement factor 4, classical activation pathway | Association study | SCZ (n = 28,799) vs.. Con (n = 35,986) | Sekar et al. (2016) |
| IL10 | 1q32.1 | interleukin 10 | Cytokine produced by monocytes and lymphocytes | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| Inflammation & HPA axis | ||||||
| IL1B | 2q14.1 | interleukin 1 beta | Potent proinflammatory cytokine | Association study | T2DM (n = 200) vs. Con (n = 223) | Achyut et al. (2007) |
| Association study | SCZ (n = 621) vs. Con (n= 531) | Kapelski et al. (2015) | ||||
| Meta-analysis | SCZ (n = 20,185) vs. Con (n = 20,542) | Hudson and Miller (2018) | ||||
| IL6 | 7p15.3 | interleukin 6 | Inflammation and the maturation of B cells | Association study | T2DM Twins (n = 6,720) | Arora et al. (2011) |
| Association study | SCZ (n = 621) vs. Con (n= 531) | Kapelski et al. (2015) | ||||
| Meta-analysis | SCZ (n = 19,022) vs. Con (n = 19,378) | Hudson and Miller (2018) | ||||
| TNF | 6p21.33 | tumor necrosis factor | Encodes a multifunctional proinflammatory cytokine | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| Oxidative stress | ||||||
| GSTM1 | 1p13.3 | glutathione S-transferase mu 1 | Conjugattes reduced glutathione to hydrophobic electrophiles Detoxification of electrophilic compounds | Association study | SCZ (n = 111) vs. Con (n = 130) | Pae et al. (2004) |
| Association study | SCZ (n = 138) vs. Con (n = 133) | Gravina et al. (2011) | ||||
| GWAS | SCZ and T2DM database | Liu et al. (2013) | ||||
| Meta-analysis | T2DM (n = 1,354) vs. Con (n = 1,666) | Tang et al. (2013) | ||||
| Meta-analysis | T2DM (n = 2,577) vs. Con (n = 4,572) | Zhang et al. (2013) | ||||
| GSTT1 | 22q11.23 | glutathione S-transferase theta 1 | Conjugates reduced glutathione to hydrophobic electrophiles Detoxification of electrophilic compounds | Association study | SCZ (n = 138) vs. Con (n = 133) | Gravina et al. (2011) |
| Meta-analysis | T2DM (n = 1,271) vs. Con (n = 1,470) | Tang et al. (2013) | ||||
| Meta-analysis | T2DM (n = 2,577) vs. Con (n = 4,572) | Zhang et al. (2013) | ||||
| MTHFR | 1p36.22 | methylenetetrahydrofolate reductase | Catalyzes conversion of methylenetetrahydrofolate | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| PON1 | 7q21.3 | paraoxonase 1 | Hydrolyzes toxic metabolites | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| SOD2 | 6q25.3 | superoxide dismutase 2 | Destroys superoxide anion radicals | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| TXNRD2 | 22q11.21 | thioredoxin reductase 2 | Regulation of mitochondrial redox homeostasis | CNV analysis | Cumulative scoring evidence,based on 32 CNV studies in SCZ | Luo et al. (2014) |
| Association study | T2DM patients with myocardial infarction (n = 166) vs. Con (n = 811) | Kariž et al. (2015) | ||||
| UCP2 | 11q13.4 | uncoupling protein 2 | Mitochondrial transporter protein | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| Prolactin pathway | ||||||
| NPY | 7p15.3 | neuropeptide Y | Control of feeding, secretion of gonadotrophin-release hormone | Association study | SCZ (n = 212) vs. Con (n = 199) | Itokawa et al. (2003) |
| Association study | T2DM (n = 263) vs. Con (n = 469) | Nordman et al. (2005) | ||||
| GWAS | SCZ and T2DM database | Liu et al. (2013) | ||||
| PRL | 6p22.3 | prolactin | Encodes anterior pituitary horomone prolactin | Association study | SCZ (n = 403) vs. Con (n = 653) | Rybakowski et al. (2012) |
| Other | ||||||
| DLGAP1 | 18p11.31 | DLG associated protein 1 | Scaffold protein in postsynaptic density, glutamate neurotransmission | CNV analysis | SCZ (n = 662) vs. Con (n = 2,623) | Kirov et al. (2012) |
| CNV analysis | T2DM (n = 1,715) | Prabhanjan et al. (2016) | ||||
| Herv K-18 | 1q23.3 | endogenous retrovirus group K member 18 | CD48 signaling lymphocyte activating (SLAM) gene | Association study | SCZ with T2DM (n = 29) vs. SCZ (n = 200) | Dickerson et al. (2008) |
| IGF2BP2 | 3q27.2 | insulin-like growth factor 2 mRNA binding protein 2 | Embryonic growth and development, decrease insulin secretion | Association study | T2DM (n = 2,201) | Lyssenko et al. (2008) |
| Association study | SCZ (n = 790) vs. Con (n = 1,083) | Zhang et al. (2013b) | ||||
| PACRG | 6q26 | parkin coregulated | Molecular chaperone/chaperonin-binding | GWAS | SCZ (n = 924), T2D (n = 822), comorbid (n = 505); controls (n = 1,125) | Hackinger et al. (2018) |
| PSMD9 | 12q24.31 | proteasome 26S subunit, non-ATPase 9 | Chaperone of 26S proteasome complex assembly Insulin gene transcription coactivator |
Association study | T2DM affected siblings/families (n = 201) | Gragnoli (2010) |
| Association study | SCZ (n = 1,351) vs. Con (n = 1,378) | Lee et al. (2013) | ||||
| SRR | 17p13.3 | serine racemase | Catalyzes synthesis of D-serine | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| SYN2 | 3p25.2 | synapsin Ⅱ | Synaptogenesis, modulation of neurotransmitter release | GWAS | SCZ and T2DM database | Liu et al. (2013) |
| TSPAN18 | 11p11.2 | tetraspanin 18 | Tetraspanin families which regulate cell development | GWAS | SCZ and T2DM database | Liu et al. (2013) |