Estimating and Correcting Optimism Bias in Multivariate PLS Regression: Application to the Study of the Association Between Single Nucleotide Polymorphisms and Multivariate Traits in Attention Deficit Hyperactivity Disorder

Abstract Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

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The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Psychiatry Investigation ◽

10.30773/pi.2017.07.24 ◽

2018 ◽

Vol 15 (3) ◽

pp. 306-312 ◽

Cited By ~ 1

Author(s):

Hui-Ching Huang ◽

Lawrence Shih-Hsin Wu ◽

Shun-Chieh Yu ◽

Bo-Jian Wu ◽

Ahai Chang Lua ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Single Nucleotide Polymorphism ◽

Children And Adolescents ◽

Attention Deficit ◽

Adrenergic Receptor ◽

Receptor Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Hyperactivity Disorder ◽

Adrenergic Receptor Gene

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Acetylcholine-metabolizing butyrylcholinesterase (BCHE) copy number and single nucleotide polymorphisms and their role in attention-deficit/hyperactivity syndrome

Journal of Psychiatric Research ◽

10.1016/j.jpsychires.2013.08.006 ◽

2013 ◽

Vol 47 (12) ◽

pp. 1902-1908 ◽

Cited By ~ 12

Author(s):

Christian P. Jacob ◽

Heike Weber ◽

Wolfgang Retz ◽

Sarah Kittel-Schneider ◽

Julia Heupel ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Attention Deficit ◽

Copy Number ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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CLOCK Polymorphisms in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence Linking Sleep and Circadian Disturbances and ADHD

Genes ◽

10.3390/genes10020088 ◽

2019 ◽

Vol 10 (2) ◽

pp. 88 ◽

Cited By ~ 4

Author(s):

Marina Carpena ◽

Mara Hutz ◽

Angélica Salatino-Oliveira ◽

Guilherme Polanczyk ◽

Cristian Zeni ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Circadian Rhythm ◽

Attention Deficit ◽

Sleep Problems ◽

Clinical Sample ◽

Secondary Analysis ◽

Binary Logistic Regression ◽

Nucleotide Polymorphisms ◽

Short Sleep Duration ◽

Hyperactivity Disorder

Circadian and sleep disorders, short sleep duration, and evening chronotype are often present in attention-deficit/hyperactivity disorder (ADHD). CLOCK, considered the master gene in the circadian rhythm, has been explored by few studies. Understanding the relationship between ADHD and CLOCK may provide additional information to understand the correlation between ADHD and sleep problems. In this study, we aimed to explore the association between ADHD and CLOCK, using several genetic markers to comprehensively cover the gene extension. A total of 259 ADHD children and their parents from a Brazilian clinical sample were genotyped for eight single nucleotide polymorphisms (SNPs) in the CLOCK locus. We tested the individual markers and the haplotype effects using binary logistic regression. Binary logistic and linear regressions considering ADHD symptoms among ADHD cases were conducted as secondary analysis. As main result, the analysis showed a risk effect of the G-A-T-G-G-C-G-A (rs534654, rs1801260, rs6855837, rs34897046, rs11931061, rs3817444, rs4864548, rs726967) haplotype on ADHD. A suggestive association between ADHD and rs534654 was observed. The results suggest that the genetic susceptibility to circadian rhythm attributed to the CLOCK gene may play an important role on ADHD.

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