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Report for Clinical Trial NCT03601026

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Interdisciplinary Approach to Maximize Adolescent Potential: Genetic Counselling Interventions to Reduce Negative Environmental Effects

Severe mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Most risk factors for SMI are either unchangeable (e.g., genetics) or difficult to alter (e.g., low socio-economic status). In contrast, cannabis use is one specific risk factor that could be avoided. Certain individuals are more vulnerable to the harmful effects of cannabis. Genetic factors can help us identify these high-risk individuals. One in three individuals are carriers of a higher-risk genetic variant, and cannabis users with this genotype are at up to 7-fold increased risk of developing schizophrenia. In our study, genetic counselling will be provided to participants by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype. Participants will be counselled regarding their individualized risk of developing and of not developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if the participants accept the genetic test results). The investigators hypothesize that this intervention will reduce exposure to cannabis compared to the youth who are not offered the intervention.

NCT03601026 Mental Illness Schizophrenia Bipolar Disorder Major Depressive Disorder Cannabis Use Psychosis
MeSH: Disease Marijuana Abuse Schizophrenia Depressive Disorder Depressive Disorder, Major Bipolar Disorder Mental Disorders
HPO: Bipolar affective disorder Depressivity Mania Schizophrenia

1 Interventions

Name: Genetic counselling

Description: Participants will receive information on risk/protective factors and causes of mental illness. Participants are not required to receive numeric/genetic risk information. Participants who choose to receive genetic and/or numeric risk information will be counselled on their risk of NOT developing and of developing SMI based on their genetic test results and/or family history information they provide. Risk estimates will be derived by genetic counsellors, according to standard practice guidelines. Participants who receive genetic information will be counselled on the possible influence of cannabis use on risk of mental illness based on their genotype. Participants who choose to not receive genetic information will be counselled on the influence of cannabis on mental health.

Type: Behavioral

Genetic counselling


Primary Outcomes

Description: Self-reported cannabis use on a questionnaire.

Measure: Self-reported cannabis use

Time: 1 month

Secondary Outcomes

Description: Acceptability will be established as the proportion of individuals accepting the offer of intervention.

Measure: The proportion of participants who complete the intervention after receiving an offer to participate (intervention acceptability)

Time: Completion of study (2 years).

Description: Urine will be screened for the presence/absence of cannabinoids.

Measure: Presence of cannabinoids in urine

Time: 1 month

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 rs2494732

A replicated gene-cannabis interaction shows that carriers of a common genetic variant (C alleles at rs2494732 in the AKT1 gene) are at up to 7-fold increased risk of developing psychosis if they use cannabis.



HPO Nodes


HPO:
Bipolar affective disorder
Genes 28
TWNK RPS6KA3 TBX1 GP1BB HIRA RRM2B ARVCF FA2H SEC24C DNMT3A ATP2A2 MECP2 POLG2 CLCN4 CHRNA7 FLI1 JMJD1C SMPD1 RREB1 USP8 CDH23 CLCN4 TBX1 COMT POLG UFD1 TBX1 SLC25A4
Depressivity
Genes 377
AMACR BAZ1B PDCD1 PRKAR1A KCTD17 AFG3L2 DNAJC13 NSMF PRPH TBP DNA2 TOR1A UBQLN2 MED25 WFS1 TRNL1 ADH1C ND4 GNAS RFC2 FGF14 HMBS PLA2G6 SPAST PRKCG HTR2A SQSTM1 ATRX GABRA1 FGF8 FUS CLCN4 LMNB1 CLN6 TRNS2 GDAP2 PON2 GSN SNCA FAN1 XK TWNK PTS TRNQ RPS6KA3 TBX1 GLT8D1 OPTN PINK1 GTF2IRD1 NHLRC1 GBA TRNN PANK2 CRBN GNRH1 PSAP NDST1 GLUD2 SOD1 DNAJC6 LRRK2 DNMT1 PDE11A TAC3 DRD2 MAN1B1 HTT AP2S1 SPRY4 PGAP1 CBS SQSTM1 TOR1A AIMP1 TUSC3 PDGFB TWNK FMO3 SLC20A2 MECP2 CACNA1G CDH23 C9ORF72 FUS GPR35 TARDBP C9ORF72 HIRA IDUA HLA-DQB1 PRSS12 C9ORF72 CLIP2 PIGC HNMT JRK TRNF PAH CLRN1 ATXN2 CPOX CEP78 MSTO1 ELN CLCN4 CISD2 PROK2 PDGFB SGCE SLC6A4 KCNT1 PDGFRB UCHL1 MATR3 GABRG2 SMPD1 PRNP GNRHR KISS1R COQ2 HS6ST1 TNIK NEFH MAPT C9ORF72 ATP13A2 PARK7 NSUN2 SLC25A4 CCNF ANXA11 HLA-DQB1 TBL2 CPOX SNCAIP FIG4 TARDBP NOTCH3 LINS1 VAPB BMPR1A ARVCF SLC18A2 C19ORF12 MAPT ATXN10 POLG SLC45A1 KDM5B MST1 SEC24C B3GALNT2 MLH3 PPT1 FRRS1L JPH3 WDR11 PODXL ND6 ARMC5 HTRA2 AIP CRADD TTC19 MED23 ZC3H14 JMJD1C PRNP USH2A ATP1A3 TRNS1 ND5 EDC3 COASY UNC13A COMT UFD1 VCP POLG FMR1 PMS1 FMN2 PRNP PRNP CHD7 DCPS METTL23 DCTN1 TRNL2 GBA PPP2R2B ATP7B GTF2I USH1G PTPN22 SRPX2 TACR3 TWNK GNA11 TMEM106B SNCA CSF1R MLH1 TRNH PMS2 CLIP1 POLG2 ATXN8OS CASR VPS13C PON1 RSRC1 PPOX VCP HLA-DRB1 EZR DUSP6 BCS1L DCTN1 EHMT1 TRNL1 PRNP PDZD7 MSH6 MAPT EPHA4 POLG THOC2 CRKL CYP27A1 PLA2G6 ANG CC2D1A DCTN1 MYO7A CACNA1H HTT DNAJC5 COQ2 GRIN2A GP1BB DGUOK PRKN CHMP2B KRAS ARSA NR4A2 HNRNPA1 CHMP2B WASHC4 TRNS2 ATXN10 MSH2 CFAP410 PFN1 HMBS CACNA1G GNAS MYO7A SLC2A1 PINK1 POLG C9ORF72 PSEN1 ANOS1 PIK3CA ALMS1 TBC1D7 VCP TRNS1 PANK2 GBA TK2 LIMK1 CHCHD10 XPR1 PPARGC1A RPS20 USP8 ST3GAL3 ARMC5 HARS1 KCTD17 TAF15 AARS2 PER3 FGF14 CTSF TBP MECP2 MBOAT7 POLG PAH TREM2 USH1C TREM2 COX1 TBK1 C12ORF4 WARS2 STX16 ATXN8 SGCE ND1 ATXN8OS PRKACA TBK1 ARSG MAPK1 ATXN2 GRN ABCA7 OCRL KCNJ2 TRNW CHCHD10 COX3 RREB1 DAO GIGYF2 GPR101 TECR CDH23 ATP1A3 EPCAM ADGRV1 GNAS TCF4 GNAS GABRG2 PRNP KISS1 TGFBR2 SEMA4A TWNK GCH1 CIB2 COX2 FGFR1 PCDH15 WHRN LRRK2 TRAPPC9 RRM2B FMR1 RRM2B WFS1 FA2H FGF17 HBB PDGFRB SARS1 BCR EIF4G1 POLG ERBB4 GLA PER2 FBXO31 PON3 GLE1 PROKR2 VPS35 NEK1 MSTO1 LMAN2L GNAS DNMT1 GABRB3 CP TBX1 EPM2A PDGFRB GRIK2 SNCA VCP
Mania
Genes 29
TWNK RPS6KA3 TBX1 GP1BB HIRA RRM2B ARVCF FA2H SEC24C DNMT3A ATP2A2 MECP2 POLG2 CLCN4 CHRNA7 FLI1 JMJD1C SMPD1 RREB1 USP8 CDH23 SLC25A13 CLCN4 TBX1 COMT POLG UFD1 TBX1 SLC25A4
Schizophrenia
Genes 71
USH1C RTN4R USH1G HIRA UPF3B GJA5 DNAJC13 DNMT3A KRT86 HTR2A APOL4 CLRN1 DRD3 CEP78 ARSG MSTO1 TRNE PRODH RREB1 GIGYF2 PDZD7 MTHFR RBM12 ADGRV1 NKX2-1 TRNS2 KRT83 SNCA MYO7A COMT CIB2 PCDH15 WHRN TBX1 GP1BB DSG4 ZDHHC9 ARSA ARVCF WFS1 PRODH PSAP APOL2 SEC24C KRT81 LRRK2 CHI3L1 MYO7A ATP2A2 SHANK3 SYN2 EIF4G1 CHRNA7 GBA FLI1 MED12 VPS35 JMJD1C MSTO1 USH2A AKT1 GJA8 TBX1 COMT UFD1 PRODH DISC2 TBX1 HARS1 CDH23 DAOA