Panic disorder and serotonergic genes (SLC6A4, HTR1A and HTR2A): Association and interaction with childhood trauma and parenting.
OBJECTIVE
The aim of this study is to evaluate the association between HTR1A, HTR2A and the 5-HTTLPR in panic disorder (PD) patients and controls. In addition, this study also aims to evaluate the interaction between these genes and two environmental factors previously associated with PD: childhood trauma and parental bonding.


METHODS
This is a case-control candidate gene association study (107 PD patients and 125 controls). Genes were analyzed using a gene-based test in PLINK followed by single marker association tests and haplotype test only for genes that reached experiment-wide significance in the gene-based test in order to minimize multiple testing. Logistic regression was used to test the relationships between genotype in the additive model, trauma, optimal paternal parenting and optimal maternal parenting and their interactions.


RESULTS
Only HTR1A was associated with PD in gene-based test after correction for multiple tests (p(corrected)=0.027) and one HTR1A haplotype comprising four SNPs was associated with PD (p(corrected)=0.032). In the interaction analysis, no significant gene-environment interaction was found with the genes evaluated.


CONCLUSIONS
This study reinforces the association between HTR1A and PD. No major evidence of gene-environment interaction in PD with parenting or trauma was found. Further studies are necessary in order to confirm these findings.
Blaya
Carolina
C
Anxiety Disorders Program, Hospital de Clínicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, Luiz Manoel Gonzaga, 630/11, 90470-280 Porto Alegre, RS, Brazil.
Salum
Giovanni A
GA
Moorjani
Priya
P
Seganfredo
Ana Carolina
AC
Heldt
Elizeth
E
Leistner-Segal
Sandra
S
Smoller
Jordan W
JW
Manfro
Gisele Gus
GG
D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002649:Child Abuse; D002650:Child Abuse, Sexual; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000235:genetics* / Q000523:psychology*; D016487:Parenting; D011110:Polymorphism, Genetic; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A