SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT00570583

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression

Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. This highlights the importance of identifying and treating CI in LDD; however, current lack of reliable prognostic information from clinical, neuroimaging, and genetic data impedes research on targeted prevention and treatment. Two critical ways to close current knowledge gaps in predicting cognitive diagnostic outcomes of LLD involve: 1) increasing the number of diagnostic cases available to existing studies, and 2) using those studies to identify clinical, imaging, and genetic predictors that will improve future diagnosis. We intend to do both in the current proposal. We plan to study the following SPECIFIC AIMS: Aim 1: Identify baseline clinical-behavioral predictors of cognitive diagnostic outcomes in LLD. Working hypothesis: During acute LLD, CN will be associated with more frequent EOD and higher negative life stress than PCI and AD; PCI will be associated with EOD and higher frailty than CN and AD; AD will be associated with LOD, greater appetite loss, lower anxiety, and greater memory impairment than CN and PCI. Aim 2: Use multimodal neuroimaging at baseline to identify patterns associated with cognitive diagnostic outcomes in individuals with LLD. Working Hypothesis: CN will be associated with greater white matter integrity compared with PCI and AD; PCI will be associated with lower white matter integrity and network abnormalities in anterior cingulate cortex compared with CN; AD will be associated with lower hippocampal volume compared with CN and PCI. Aim 3: (exploratory): Explore interrelationships among candidate genes, cognitive diagnostic outcomes, and proposed phenotypic components relevant to LLD. Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss.

NCT00570583 Major Depression Dementia
MeSH: Dementia Depression Depressive Disorder
HPO: Dementia Depressivity


Primary Outcomes

Measure: Change in Depression status (measured by Montgomery Asberg Depression Rating Scale)

Time: Minimum of once per year, up to 21 years

Measure: Change in Cognitive impairment (as measuring using cognitive tests including those found in the CERAD battery)

Time: Once per year, up to 21 years

Measure: Development of dementia (Determined by Clinical Consensus Conference)

Time: once per year, up to 14 years

Secondary Outcomes

Measure: Change in Cognition (as measured by tests including those in the CERAD battery) Change in Brain MRI markers (e.g., volume of white matter and gray matter lesions)

Time: once per year, up to 21 years

Measure: Change in Impairment in Instrumental or Basic Activities of Daily Living

Time: at least once per year, up to 21 years

Measure: Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies

Time: once post-mortem

Time Perspective: Prospective

Case-Control


There is one SNP

SNPs


1 V158M

Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss. --- val158met ---

Specifically, CN individuals will have earlier first onset of depression (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. --- val158met ---



HPO Nodes


HPO:
Dementia
Genes 277
TIMM8A ATXN2 PRICKLE1 GRN SLC13A5 ZFYVE26 WDR45 POLG CHMP2B CYP27A1 DNAJC13 ND1 OPA1 TREM2 SNCA TBP TRNS1 SQSTM1 WFS1 TREM2 ADH1C APOE TYMP PLA2G6 SPAST RNF216 FUS CLN6 ERCC4 PSEN1 COX2 HTRA1 TARDBP SNCA TRNQ NDP PINK1 IRF6 NHLRC1 VPS13C GBA ND6 PANK2 DNMT1 PSAP HNRNPA1 GLUD2 DNAJC6 LRRK2 MECP2 ITM2B NOS3 HTT SQSTM1 ATXN2 SQSTM1 MAPT GRN APP NOTCH2NLC ATP6V1E1 KCTD7 TRNV SDHA MAPT COX3 GBA2 RAB39B TREM2 ROGDI WFS1 SNCA TYROBP C9ORF72 NPC2 MAPT PNPLA6 NHLRC1 TARDBP WDR45 HLA-DQB1 SCARB2 C9ORF72 TRNW HTT NPC1 ATP6 GBA2 TRNE TMEM106B MAPT RNF216 PDGFB PDGFRB UCHL1 PRNP GBA SNCA JPH3 HNRNPA2B1 LRRK2 CYTB MAPT C9ORF72 APP PARK7 APTX APP CLN3 ATP13A2 PSEN1 SDHD DNM1L ASAH1 ATXN3 SNCAIP ROGDI NOTCH3 GBE1 C19ORF12 MAPT ATXN10 ATP6 JPH3 PSEN1 TTR PODXL HTRA2 COL4A1 PSEN1 APP SLC2A3 COX1 PRNP ATP13A2 APP MBTPS2 TRNF CUBN FMR1 PRNP ATP13A2 POLG DCTN1 CHMP2B TUBB4A GBA PPP2R2B SDHAF1 HEXA CST3 TWNK ATP6V0A2 GRN TMEM106B SNCA TREX1 CSF1R TRNS2 MATR3 PRNP CHMP2B AMN MAPT SNCB VPS13C ATP6V1A APP VCP MAPT CSTB DCTN1 GM2A SORL1 TRNK PRNP PRNP PSEN1 ABCD1 CP PLA2G6 HTT DNAJC5 UBQLN2 TREM2 DGUOK PRKN ARSA NR4A2 ATP13A2 CHMP2B ATN1 PRDM8 VCP PSEN1 PSEN2 PINK1 PLAU PSEN1 CISD2 TRPM7 CFAP43 CHCHD10 MPO HFE VCP GBA ATP7B XPR1 ITM2B TUBA4A FTL HNRNPA2B1 CERS1 AARS2 CTSF TBP SERPINI1 MATR3 TRNL1 SPG21 PPP2R2B TREM2 TBK1 CHMP2B ABCA7 TYROBP EPM2A TRNC VPS13A ALDH18A1 NOTCH3 ATXN8OS ATXN2 TOMM40 GRN FTL CHCHD10 TMEM106B VCP GIGYF2 C9ORF72 PRNP APOE PSEN2 FBXO7 SDHB ADA2 LRRK2 PANK2 FMR1 PRKAR1B C9ORF72 ND5 MAPT EIF4G1 CFAP43 APP VPS35 SPG21 ERCC8 VCP DNMT1 MMACHC A2M CP HTRA1 TBK1 ASAH1 ALDH18A1 ATN1 RRM2B EPM2A GBA PRDX1 SNCA VCP
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