Stress-related genetic components in attention-deficit/hyperactivity disorder (ADHD): Effects of the SERPINA6 and SERPINA1 genetic markers in a family-based brazilian sample

SERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus–Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying...

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Published in:Journal of psychiatric research 2022-05, Vol.149, p.1-9
Main Authors: Carpena, Marina Xavier, Sánchez-Luquez, Karen Yumaira, Martins-Silva, Thais, Santos, Thiago M, Farias, Cid Pinheiro, Leventhal, Daniel Gray Paschoal, Berruti, Barbara, Zeni, Cristian Patrick, Schmitz, Marcelo, Chazan, Rodrigo, Hutz, Mara H., Salatino-Oliveira, Angélica, Genro, Julia P., Rohde, Luis Augusto, Tovo-Rodrigues, Luciana
Format: Article
Language:English
Subjects:
ADHD
alpha 1-Antitrypsin - genetics
Attention Deficit Disorder with Hyperactivity - genetics
Brazil
Cortisol
Genetic Markers
Genotype
GWAS
HPA axis Dysregulation
Humans
Hydrocortisone - metabolism
Polymorphism, Single Nucleotide
SERPINA6
Transcortin - genetics
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Summary:SERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus–Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying this relationship are still unclear. Evaluation of the SERPINA6/SERPINA1 gene cluster in ADHD may provide relevant information to uncover them. We tested the association between the SERPINA6/SERPINA1 locus, including 95 single nucleotide polymorphisms (SNPs), and ADHD, using data from a Brazilian clinical sample of 259 ADHD probands and their parents. The single SNP association was tested using binary logistic regression, and we performed Classification and Regression Tree (CART) analysis to evaluate genotype combinations' effects on ADHD susceptibility. We assessed SNPs’ regulatory effects through the Genotype-Tissue Expression (GTEx) v8 tool, and performed a complementary look-up analysis in the largest ADHD GWAS to date. There was a suggestive association between ADHD and eight variants located in the SERPINA6 region and one in the intergenic region between SERPINA6 and SERPINA1 after correction for multiple tests (p 
ISSN:0022-3956
1879-1379
DOI:10.1016/j.jpsychires.2022.02.014