SNPMiner Trials by Shray Alag


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Report for SNP rs1549339

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 The Impact of Supplementation With Multi-vitamins/Minerals, With and Without Fatty Acids, on Impulsivity and Aggression

There is a series of well designed studies that have reported, in those with a history of anti-social behavior, that supplementation with vitamins / minerals, omega-3 fatty acids (n-3 FA), or both, reduces the incidence of aggressive behavior. Although there is evidence that all these nutrients have a role, to date the relative contribution of fatty acids and vitamins / minerals has not been considered: for example the possibility of a synergistic interaction has not yet been examined. In addition the topic has to date been studied under real-life condition, such as a prison, making the topic difficult to study. The major aim of the present study was to develop a paradigm that would allow the study of the topic in a sample from the general population without a history of anti-social behavior. Subjects received either a vitamin/mineral supplement, a fatty acid supplement, both or neither for three months, Measures of impulsivity and aggression were assessed before and after supplementation. Although in the past measures of actual behaviour have proved to be sensitive to supplementation, questionnaire measures have not. The second major objective was therefore to consider whether such phenomena can be studied in a sample without a history of anti-social behavior, using standardized, sensitive laboratory based measures and to compare these with questionnaire measures. POLYMORPHISMS AND THE RESPONSE TO MICRO-NUTRIENT SUPPLLMENTATION The data set were subsequently used to test an a priori hypothesis not related to the initial hypothesis. A meta-analysis found a consistent pattern that micro-nutrient supplementation improved mood (Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med 2013; 75: 144-153). To produce evidence of possible mechanisms the extent was determined, to which the impact of micro-nutrient supplementation was influenced by a range of polymorphisms associated with neurotransmitter systems known to modulate mood. The primary outcome measure was the General Health Questionnaire, a 30-item self-report questionnaire that was developed to detect, in a community sample, those who would benefit from seeing a psychiatrist. Given the literature that relates polymorphisms to mood disorders, and the known pharmacology of anti-depressant drugs, a range of polymorphisms were chosen associated with serotonin and catecholamines. Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946); Catechol-O-methyltransferase (COMT, rs4680, rs6269). Dopamine receptor D1 (DRD1, rs4532); Dopamine receptor D2 (DRD2, rs1079598, rs1800497); Dopamine receptor D3 (DRD3, rs6280); Dopamine receptor D4 (DRD4, rs1800955). Serotonin Ten SNPs associated with different aspects of serotonin metabolism were also considered. Rs1843809 is a SNP of the TPH2 gene that encodes Tryptophan hydroxylase. Rs1050565 is a SNP in the BLMH gene that influences the activity of 5HTT (SLC6A4), the serotonin transporter. SNPs associated with various serotonin receptors were also examined: genetic variations of the HTR1A gene (5-HT1A receptor, rs6295); HTR1B gene (5-HT1B receptor, rs6296); HTR2A gene (5-HT2A receptor, rs6311); HTR2B gene (5-HT2B receptor, rs1549339); HTR2C gene (5-hydroxytryptamine receptor 2C, rs518147); HTR3A gene (5-hydroxytryptamine receptor 3A, rs1150226); HTR3B (5-HT3B receptor, rs1672717); HTR4 gene (5-HT4 receptor, rs2278392). Adrenergic mechanisms Finally six SNPs associated with adrenergic receptors were considered: ADRA2A (adrenoceptor alpha 2A, rs553668); ADRB1 (adrenoceptor alpha B1, rs1801253); ADRB2 (adrenoceptor alpha B2, rs1042713; ADRB3 (adrenoceptor alpha B3, rs4994); SLC6AC (noradrenaline transporter, rs5569 and rs2242447). Analysis The data will be analyzed using analysis of variance with a change in GHQ from before to after supplementation as the dependent variable: Micronutrient/placebo X Polymorphism.

NCT01558193 Aggression Dietary Supplement: Placebo Dietary Supplement: Multi-vitamin/mineral Dietary Supplement: Docosahexaenoic acid Dietary Supplement: DHA plus vitamins/minerals
MeSH: Aggression Impulsive Behavior
HPO: Aggressive behavior Impulsivity

SNPs associated with various serotonin receptors were also examined: genetic variations of the HTR1A gene (5-HT1A receptor, rs6295); HTR1B gene (5-HT1B receptor, rs6296); HTR2A gene (5-HT2A receptor, rs6311); HTR2B gene (5-HT2B receptor, rs1549339); HTR2C gene (5-hydroxytryptamine receptor 2C, rs518147); HTR3A gene (5-hydroxytryptamine receptor 3A, rs1150226); HTR3B (5-HT3B receptor, rs1672717); HTR4 gene (5-HT4 receptor, rs2278392).

Primary Outcomes

Description: The GoStop Impulsivity Paradigm measures the ability to inhibit an already initiated response. A number of five digits are presented on a computer screen for 500ms followed by a 500ms blackout. A second number then appears for 500ms followed by a 500ms blackout. If the numbers are identical the mouse button has to be pressed before the second number disappeared. However, the response has to be with-held if a "Stop" signal appeared; that is the second number was identical but changed from black to red. If the two numbers were different then no response was required.

Measure: Go Stop Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: This is test of the tendency to respond in an aggressive manner. A series of cartoons are presented that present an intentionally frustrating situation. The participant reports what he or she would say in that situation. Blind the responses are assessed in terms of the extent to which the responses are aggressive in matter Note that the use of two primary outcomes reflects the aim of the study to contrast performance and questionnaire measures

Measure: Rosenzweig Picture Frustration Test

Time: Change from before to after supplementation for three months

Secondary Outcomes

Description: The Buss-Perry Aggression Questionnaire assesses four aspects of aggressive behavior: physical aggression, verbal aggression, anger and hostility. Participants rank statements about their temperament using a 7-point Likert scale ranging from 1 (extremely uncharacteristic of me) to 7 (extremely characteristic of me).

Measure: Buss Perry Aggression Scale

Time: Change from before to after supplementation for three months

Description: The Perceived Stress Scale assesses the extent to which stressful thoughts and feeling had been experienced during the last month. For example: "In the last month, how often have you been upset because of something that happened unexpectedly?" The participant responded on a scale ranging from 0 = Never to 4 = Very Often. An overall score is calculated.

Measure: Perceived Stress Scale

Time: Change from before to after supplementation for three months

Description: A measure of the subjects ability to forgo initial reward for a later larger reward. The subject can choose to wait for a reward and get more points or alternatively respond more quickly and get fewer points sooner. The longer a subject waits the higher the reward; that the more points are earned. A mouse click began the task and a second resulted in a reward. Two counters display the most recent and cumulative reward over a 20 minute session. Subject are able to infer that responses at a faster rate earn smaller rewards.

Measure: Single Key Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: Polymorphisms associated with the metabolism and receptors of dopamine and serotonin will be related to the response to micro-nutrient supplementation

Measure: General Health Questionnaire

Time: Further analysis of existing data - considers changes from baseline to three months


HPO Nodes


Aggressive behavior
Genes 203
GRN ARID1B NONO WDR45 ZMYND11 EHMT1 CHMP2B SLC6A1 EIF2S3 UBE2A TREM2 UROC1 NDST1 PRODH KDM5C ALDH5A1 SPAST GABRB3 SMARCC2 HDC CPLX1 EEF1A2 SLC25A13 CLCN4 BPTF MYT1L SCN1A DHCR7 TIMM50 TBX1 MAOA LEPR NDP GRIA3 TRIO PHIP OCRL TRIP12 WDR62 SATB2 EBP CUL4B SQSTM1 ADAT3 TBC1D24 RORB CAMTA1 SOX5 INPP5E ANK3 DGCR2 FIG4 PIGH AP1S2 WDR45 LINGO1 NRXN1 MANBA CNTNAP2 KIF11 PAH PAK3 LINS1 TMEM106B CLCN4 MAPT KMT2A MAN1B1 KCNT1 ESS2 SHANK3 SASS6 KDM5C GABRD SMC1A NAGS SATB2 KMT2E NAGLU CLCN2 PUS7 SLC6A17 PSMD12 NSDHL TCF4 AFF2 AP2M1 RLIM TIMM50 DGCR6 ENTPD1 GABRA1 HSD17B10 DYNC1I2 NFIB FOXP1 TTC19 ADSL MAB21L1 PRNP TMEM240 DDX3X NONO DEAF1 DEAF1 PRRT2 NAA10 ATP13A2 CAMTA1 PTCHD1 KNL1 ATP7B MGAT2 RBBP8 DNMT3A C12ORF4 SPR PCDH19 RUSC2 KCNQ3 PACS1 EEF1A2 SLC52A3 DDX3X PSEN1 SH2B1 TMEM231 TTI2 PLA2G6 SARS1 SLC2A1 BCOR ATP13A2 ATXN10 VCP HNRNPH2 CEP152 SYN1 TCF4 GAMT GCSH SLITRK1 MED12 CHD2 FGF14 ADNP TBP DPYD SETD2 TRIO DPAGT1 WAC KMT2A NSDHL IMPA1 CHMP2B TYROBP GRIA3 VPS13A DGCR8 CTNNB1 MAPK10 AFF2 TCF4 SLC52A2 HERC2 PCDH19 UBE2A C9ORF72 SIN3A EFHC1 SLC6A8 PRNP AMT ZBTB20 NFASC USP9X FRMPD4 BCAP31 CUX2 CACNB4 PIGY ECM1 POGZ ELP2 JRK TCF20 MECP2 CNTNAP2 SMARCA2 UQCC2 ENTPD1 CUL4B WARS2 MBD5 ANK3 AP1S2 DNM1 CILK1 SLC52A2 GLDC SYN1 CHD2
Impulsivity
Genes 126
PTCHD1 KNL1 DHDDS SLC13A5 AARS1 SCN8A FUZ SLC6A1 SNCA DNAJC13 KCNA2 CLIP1 MED25 MAGEL2 PARS2 VPS13C AP3B2 RSRC1 CLTC EZR PLA2G6 GABRA2 ARV1 CC2D1A SNCA YWHAG MAOA PRKN CACNA1B UBA5 NECAP1 WASHC4 CRBN HIVEP2 DNMT1 PHIP NDST1 SCN3A DNAJC6 WDR62 LRRK2 PINK1 CEP152 VANGL1 MAN1B1 PANK2 GBA PGAP1 AIMP1 TUSC3 GCSH TRAK1 GABRG2 ST3GAL3 SYNGAP1 CHD2 HCN1 CACNA1A MBOAT7 WWOX CYFIP2 GRIN2D GABRB2 MAPT DNM1 KCNA2 C12ORF4 WARS2 PRSS12 PIGC HNMT AFF2 EP300 GABRA5 PPP3CA UCHL1 GIGYF2 TECR PCDH19 TNIK PARK7 NSUN2 NUS1 AMT SZT2 FGF12 SLC1A2 LRRK2 TRAPPC9 LINS1 STXBP1 EEF1A2 AFF2 ACTL6B AP2M1 C19ORF12 CNKSR2 SLC45A1 KDM5B B3GALNT2 NTRK2 FRRS1L SARS1 PODXL HTRA2 EIF4G1 CRADD FBXO31 KCNB1 MED23 ZC3H14 VPS35 ATP6V1A TMEM240 LMAN2L CREBBP CLTC EDC3 GLDC KANSL1 FMN2 SYNJ1 CNKSR2 GRIK2 DCPS METTL23