SNPMiner Trials by Shray Alag


SNPMiner Trials: SNP Report


Report for SNP rs6295

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

There are 2 clinical trials

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

2 Inflammation Och hjÀrnfunktion - Huvudstudie

In this randomized double blind study, 52 healthy participants were injected with either 0.6 ng/kg body weight or placebo to test if changes in pain sensitivity is associated with change in neural activity using BOLD MR scanning.

NCT03551184 Sickness Behavior Biological: Endotoxin Biological: Placebo
MeSH: Inflammation Illness Behavior

The study and the procedures used in the study are described in detail here: https://openarchive.ki.se/xmlui/bitstream/handle/10616/44650/Thesis_Bianka_Karshikoff.pdf?seq uence=8&isAllowed=y The following papers using data from this study is published: Lindstedt F, Karshikoff B, Schalling M, Olgart Hoglund C, Ingvar M, Lekander M & Kosek E. Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception.

Primary Outcomes

Description: Both deep and cutaneous pain at threshold and suprathreshold noxious levels. Heat- and cold (cutaneous) pain sensitivity was assessed for threshold stimuli and intense noxious stimuli, as well as pressure (deep) pain thresholds and CPM (descending pain inhibition).

Measure: Pain sensitivity (cutaneous and deep)

Time: 7.5 hours

Description: BOLD activity from MR scans Functional connectivity of the insular cortex during acute inflammation, in relation to symptoms of sickness. Changes in central pain mechanism during acute inflammation, assessed as activity in the insula and areas of the descending pain inhibitory pathways in the brain. Changes in brain function during an emotional task with an interoceptive component during acute inflammation.

Measure: Brain function

Time: 7.5 hours

Secondary Outcomes

Description: "How is your health right now?" rated on a 7 point Likert scale at baseline, after 90 minutes and after 4.5 hours. "How do you rate your general state of health?" rated on a 5-point Likert scale at 90 minutes post-injection

Measure: Self-rated health

Time: 4.5 hours

Description: Photos were taken under standardised conditions before and after injection

Measure: Facial appearence

Time: 2 h


HPO Nodes


Aggressive behavior
Genes 157
MYT1L PIGY CUL4B GABRB3 GABRD SOX5 DPAGT1 DGCR2 NDST1 TCF4 DPYD C12ORF4 CACNB4 SATB2 AMT ZMYND11 CUX2 DGCR6 ZBTB20 DEAF1 ADAT3 SPAST ESS2 ATP7B IMPA1 FRMPD4 AFF2 MANBA PSEN1 ANK3 MAOA TRIO MAPT SPR RBBP8 USP9X INPP5E KDM5C SMC1A SLC6A17 TTI2 NAGLU CPLX1 NAA10 ICK NFASC GRIA3 UQCC2 GRN CHD2 NDP SIN3A PSMD12 UROC1 OCRL GCSH PRRT2 BCOR ECM1 TRIP12 ATP13A2 MECP2 SLITRK1 SHANK3 WARS2 LEPR SLC2A1 SH2B1 NAGS HNRNPH2 DDX3X TTC19 TBC1D24 CHMP2B WAC RUSC2 EEF1A2 NSDHL SLC52A3 SLC6A1 SLC6A8 TMEM106B TYROBP BPTF PACS1 LINS1 WDR45 SETD2 ARID1B BCAP31 EFHC1 MGAT2 UBE2A CLCN2 SARS ADSL CLCN4 LINGO1 PIGH FIG4 GLDC NFIB SQSTM1 EIF2S3 SCN1A JRK DHCR7 PCDH19 ENTPD1 RLIM PAH VPS13A CNTNAP2 TIMM50 TREM2 SMARCA2 EHMT1 SYN1 PAK3 SASS6 AP1S2 KMT2A SMARCC2 KCNQ3 PLA2G6 FOXP1 ELP2 FGF14 CEP152 HSD17B10 ATXN10 DGCR8 HERC2 SLC52A2 CAMTA1 TMEM231 DNM1 C9ORF72 MBD5 MAPK10 NONO ALDH5A1 KCNT1 PHIP MED12 TBX1 MAN1B1 PUS7 PRNP WDR62 VCP TMEM240 KIF11 PRODH GABRA1 KNL1 TBP
Impulsivity
Genes 65
GABRB2 SLC6A1 CACNA1A UBA5 ATP6V1A AARS AMT DNAJC13 MAGEL2 PANK2 HIVEP2 KCNA2 PPP3CA STXBP1 WWOX AFF2 KANSL1 MAOA KCNB1 ARV1 SYNJ1 SZT2 MAPT GLDC VANGL1 HCN1 NTRK2 C19ORF12 PCDH19 NUS1 SCN3A AP3B2 VPS35 CLTC EIF4G1 LRRK2 SCN8A GBA FUZ GIGYF2 DHDDS SLC13A5 PLA2G6 FGF12 CHD2 CNKSR2 CEP152 GRIN2D GCSH SNCA DNM1 SLC1A2 CREBBP YWHAG PHIP EP300 CYFIP2 WDR62 TMEM240 NECAP1 DNMT1 TRAK1 KNL1 EEF1A2 SYNGAP1