Table 1.

A list of with genetic variants from multiple dopaminergic genes used in GARS and their association with PTSD including the study findings and phenotype, the gene, the association, and references (superscript citations).

DRD1:
Polymorphism	Study Findings and Phenotype	References	Comments
rs5326-A allele at the promoter region of dopamine receptor D1 (DRD1) locus CHR5	Poor strategic Planning Poor logic or judgment	Tsang et al. 2015[47]	Poor logic or poor cognitive strategic planning leads to PTSD
rs4532	Deficit in attention, avolition	Minichino et al.2017[48]	Poor focus and lack of goals can exacerbate PTS behaviors
rs4532	Impulse Control Disorder	Zainal et al. 2015[49]	Impulse control underpins PTSD behaviors
rs4532	Association with Alcohol dependence	Prasad et al. 2013[50]	Alcoholism is highly comorbid with PTSD
rs4532	Reduced post-heroin Dependence pleasure	Zhu et al. 2013[50]	Important diagnostic feature of PTSD is anhedonia
rs4532	Urbanicity upbringing alters PFC function	Reed et al. 2018[51]	Urbanicity in DRD1 polymorphic an antecedent for Psychiatric disorders
DRD2:
Polymorphism	Study Findings and Phenotype	References	Comments
rs1800497	Linkage disequilibrium A1 allele	Comings et al.,1996[35]	A1 allele confers high risk for PTSD, and A2 allele protects
rs1800497	Reduces dopamine homeostasis in PTSD Zhang et al., 20188	Zhang et al., 2018[44]	Interaction with COMT confers PTSD risk
rs1800497	Significantly associates with PTSD risk	Li et al., 2016[46]	Based on a meta-analysis
rs12364283	Associated high risk for PTSD in psychostimulant abuse	Nelson et al., 2014[19]	War Veterans Cohort
rs1800497	A1 allele magnifies PTSD severity	Hemmings et al., 2013[52]	South African Cohort
single nucleotide polymorphism (SNP) (957C>T)	Significant association PTSD risk	Voisey et al., 2009[53]	War Veterans Cohort
rs1800497	Carriers of A1 allele increased Mississippi Scale for Combat PTSD score	Lawford et al., 2006[54]	Combat Veterans with DRD2 show severe PTSD symptoms
DRD3:
Polymorphism	Study Findings and Phenotype	References	Comments
rs6280	Aberrant decision-making	Rajan et al., 2018[55]	DRD3 polymorphism will exacerbate poor decision-making in PTSD
rs6280	significantly associated with Bruxism	Oporto et al., 2018[56]	There is a high comorbidity of Bruxism and PTSD
rs6280	carrying the Ser9Gly variant associates with poor social conformity	Zhao et al., 2016[57]	People with PTSD have an inability to for social conformity style
rs6280	significant association with alcohol dependence (AD)	Kang et al., 2014 [58]	High co-morbidity of AD and PTSD
rs6280	reduced executive function	Bombin et al., 2008[59]	Poor decision-making is comorbid with PTSD
DRD4:
Polymorphisms	Study Findings and Phenotype	References	Comments
48 base repeat VNTR (Chr11 exon3) 7 R & 8R	Intense PTSD Symptoms	Dragan & Onisczenko (2009)[60]	Flood Victims Cohort
48 base repeat VNTR ( Chr11 exon3) 7R	Low Cortisol Response	Armbruster et al., 200920	Inability to respond to stressful events
48 base repeat	Low resilience to stress	Azadmarzab adi et al., 2018[61]	DRD4 7R associated with personality anxiety, depression, intelligence
48 base repeat VNTR (Chr11 exon3) 7R + R	High Life Stress	Brody et al., 2012[62]	Life Stress X DRD4 &R carriers increase drug use in African Americans
48 base repeat VNTR (Chr 11 exon 3) 7R	Association with childhood loss of trauma	Bakermans et al., 2011[63]	Carriers of the DRD4 7R have a lower ability to deal with parental
			problems which increase children’s risk for later psychopathology including PTSD
DAT1:
Polymorphisms	Study Findings and Phenotype	References	Comments
40 bases repeat VNTR (hr5,exon15) 9R	Carriers of 9R DAT1 associates with PTSD	Segman et al., 2002[64]	Dopamine genetics contribute to PTSD in Trauma Survivors
40 bases repeat VNTR (Chr5, exon 15) 9R (rs28363170) and C allele of rs27072	Children that carry the 9 R and the C allele have high PTSD following trauma than those without this haplotype	Drury et al., 2013[65]	Understanding this genetic antecedent provides future personalized epigenetic repair
40 bases repeat 9R	Anxiety traits and neuroticism	Hünnerkopf et al., 2007[66]	Interaction with harm avoidance and Neuroticism
40 bases repeat 9R	PTSD symptoms	Li et al. (2006)[46]	Meta-analysis of 19 studies
40 bases repeat 9R	PTSD symptoms	Valente et al., (2011)[67]	Post Violent Urban Victims
COMT:
Polymorphisms	Study Findings and Phenotype	References	Comments
Val158/108Met rs4680 Chr22 G allele	One or two Met copies are protective against dysfunctional working memory	Mestrovic et al., (2018)[68]	Val/ Val carriers performed worst with high delay in recall in PTSD Veterans
Val158Met	One or two copies of Met protects induces fear inhibition	Deslauriers et al., (2018) [69]	Combat Marines with PTSD
Val158Met	One or two copies of Met protects against impaired Global Functional Outcome	Winkler et al., (2017)[70]	Val variant associates with poor Global Functional Outcome
Val158Met	Trauma in preschool varies with race in African Americans Met/Met higher PTSD symptoms but in EU Caucasian Val/Val higher PTSD.	Humphreys et al., (2014)[71]	Importance of moderating influence of race on genotype
Val158Val	Carriers have a higher prediction of PTSD compared to Val158Met	Clark et al (2013)[72]	Iraq Combat Veterans
Val158Met Rs 4680	Carriers of rs4680SNP had high PTSD symptoms as part of a gene risk count of three other genes	Boscarino et al., (2012)[73]	FKBP5, CHRNA5, CRHR1and COMT contribute PTSD
MOA-A:
Polymorphisms	Study Findings and Phenotype	References	Comments
30 bases repeat VNTR Chr X Promoter 3.5R, 4R	Maltreatment in childhood in carriers MOA-A VNTR had highest PTSD aggressive type symptoms	Zhang et al. (2017)[74]	The aggression phenotype was magnified with the serotonin risk genotype
MOA-A H 3.5R and 4R	In females, not men the MOA-A – H genotype showed high aggression	Verhoeven et al., (2012)[75]	The aggression in females with high activity genotype occurs when sadness is present. Opposite evidence for MOA-A L Higher amounts of available Dopamine could lead to increased aggression especially in males
	Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L).	Frazzetto et al. (2007) 2(5):e486 [76]	Due to low activity of MAO-A increased Dopamine leads to increased aggression after trauma in childhood
5HTTLPR:(SLC6A4)
Polymorphisms	Study Findings and Phenotype	References	Comments
43 bases repeat INDEL/VNTR Chr 17 Risk alleles LG. S	Through Gene wide studies the serotonin transporter risk alleles associated with PTSD	Mehta et al., (2018) [77]	Australian and US Marine cohort
Rs25531 and risk alleles	Increased risk for PTSD in Earthquake survivors	Tian et al., (2015) [78]	Both 5-HTTLR and %-HTTVNTR polymorphisms associated with PTSD
Rs25531 and risk alleles	Increases odds of 1.5 of Combat Vets of having PTSD	Liu et al., (2015) [79]	Combat exposure cohort
Triallelic 5- HTTLPR	Homozygote SS genotype protects against PTSD re-experience of trauma	Walsh et al., (2014) [80]	African American Cohort childhood emotional abuse
Triallelic 5- HTTLPR	Homozygote SS genotype increased risk of PTSD in high trauma	Gressier et al., ( 2013) [81]	Meta-analysis mixed ethnic group
Triallelic 5- HTTLPR	Carriers of one or two copies S genotype confer increased risk of PTSD in childhood adversity	Xie et al., (2012) [82]	In a large mixed ethnic group the S genotype associated with anxiety and depression
rs16965628 (SLC6A4)	Modulated task-related ventrolateral PFC activation in PTSD	Morey et al., ( 2011) [83]	Combat related trauma
short (S)/long (L) of 5-HTTLPR (re 4795541)	Additive excess risk for frequent trauma in the L(A)/L(A) genotype	Grabe et al., (2009) [84]	60% of all L(A) allele carriers exposed to 3 or more traumas developed PTSD
Mu-Opioid Receptor (OPRM1)
Polymorphisms	Study Findings and Phenotype	References	Comments
rs1799971 Chr6 Risk allele G	G carriers increase in anger proneness hostility, ego, negative feelings	Carver et al., ( 2016) [85]	Enhanced sensitivity to negative environments loads onto PTSD
rs1799971	G carriers compared to A become more depressed when faced with social rejection	Slavich et al., (2014) [86]	Adolescent Cohort
GABRB3
Polymorphisms	Study Findings and Phenotype	References	Comments
Alpha 3 Chr15 (DNR) Risk allele 181 ( non G1)	Increased somatic symptoms, anxiety, insomnia, social dysfunction, depression	Feusner et al., (2001) [87]	Carriers non-G allele in PTSD patients show high co-morbidity

Table 1 Summary

In summary, the table depicts the exact SNPs measured in GARS and also displays a few other important SNPs not currently measured. The primary take home message is that based on an extensive literature search we have found very strong evidence of the measured SNPs in GARS and association with PTSD symptoms including:

▪ DRD1- poor strategic planning; poor logic or judgment; deficit in attention & avolition; impulse control disorder; association with alcohol dependence; reduced post-heroin dependence pleasure; urbanicity upbringing alters PFC function;

▪ DRD2- reduces dopamine homeostasis in PTSD; significantly associates with PTSD risk; associated high risk for PTSD in psychostimulant abuse; magnifies PTSD severity; increased Mississippi Scale for Combat PTSD score;

▪ DRD3- aberrant decision-making; significantly associated with Bruxism; associates with poor social conformity; significant association with alcohol dependence; reduced executive function;

▪ DRD4- intense PTSD symptoms; low cortisol response; low resilience to stress; high life stress; association with childhood loss and trauma;

▪ DAT1- increased DAT1 activity associates with PTSD; high PTSD following trauma; anxiety traits and neuroticism; high PTSD symptom;

▪ COMT- One or two Met copies are protective against dysfunctional working memory; one or two copies of Met protects against impaired Global Functional Outcome; trauma in preschool varies with race in African Americans Met/Met higher PTSD symptoms but in EU Caucasian Val/Val higher PTSD;

▪ MOA-A- maltreatment in childhood in carriers MOA-A VNTR had highest PTSD aggressive type symptoms; in females, not men the MOA-A –H genotype showed high aggression;

▪ 5HTTLPR:(SLC6A4)- through Gene wide studies the serotonin transporter risk alleles associated with PTSD; increased risk for PTSD in Earthquake survivors; increases odds of 1.5 for Combat Vets of having PTSD; homozygote SS genotype protects against PTSD re-experience of trauma; one or two copies of the S genotype confer increased risk of PTSD in childhood adversity; modulated task-related ventrolateral PFC activation in PTSD; additive excess risk for frequent trauma in the L(A)/L(A) genotype;

▪ Mu-Opioid Receptor (OPRM1)- G carriers increase in anger proneness hostility, ego, negative feelings; G carriers compared to A become more depressed when faced with social rejection;

▪ GABRB3- increased somatic symptoms, anxiety, insomnia, social dysfunction, depression.