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      BAIAP2 exhibits association to childhood ADHD especially predominantly inattentive subtype in Chinese Han subjects

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          Abstract

          Background

          Attention-deficit/hyperactivity disorder (ADHD) is a common chronic neurodevelopmental disorder with a high heritability. Much evidence of hemisphere asymmetry has been found for ADHD probands from behavioral level, electrophysiological level and brain morphology. One previous research has reported possible association between BAIAP2, which is asymmetrically expressed in the two cerebral hemispheres, with ADHD in European population. The present study aimed to investigate the association between BAIAP2 and ADHD in Chinese Han subjects.

          Methods

          A total of 1,397 ADHD trios comprised of one ADHD proband and their parents were included for family-based association tests. Independent 569 ADHD cases and 957 normal controls were included for case-control studies. Diagnosis was performed according to the DSM-IV criteria. Nine single nucleotide polymorphisms (SNPs) of BAIAP2 were chosen and performed genotyping for both family-based and case-control association studies.

          Results

          Transmission disequilibrium tests (TDTs) for family-based association studies showed significant association between the CA haplotype comprised by rs3934492 and rs9901648 with predominantly inattentive type (ADHD-I). For case-control study, chi-square tests provided evidence for the contribution of SNP rs4969239, rs3934492 and rs4969385 to ADHD and its two clinical subtypes, ADHD-I and ADHD-C. However, only the associations for ADHD and ADHD-I retained significant after corrections for multiplicity or logistic regression analyses adjusting the potential confounding effect of gender and age.

          Conclusions

          These above results indicated the possible involvement of BAIAP2 in the etiology of ADHD, especially ADHD-I.

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          Most cited references34

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          Molecular genetics of attention-deficit/hyperactivity disorder.

          Stephen V. Faraone, Roy H Perlis, Alysa E Doyle … (2005)
          Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin studies, which estimate the heritability of ADHD to be .76. Molecular genetic studies suggest that the genetic architecture of ADHD is complex. The few genome-wide scans conducted thus far are not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the eight genes for which the same variant has been studied in three or more case-control or family-based studies, seven show statistically significant evidence of association with ADHD on the basis of the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and SNAP-25.
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            Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation.

            P. Shaw, K Eckstrand, W. Sharp … (2007)
            There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
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              Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder.

              Eve Valera, Stephen V Faraone, Kate E Murray … (2007)
              Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference=.408, p<.001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.
              Article 0 comments Cited 223 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Behav Brain Funct
                Journal ID (iso-abbrev): Behav Brain Funct
                Title: Behavioral and Brain Functions : BBF
                Publisher: BioMed Central
                ISSN (Electronic): 1744-9081
                Publication date Collection: 2013
                Publication date (Electronic): 30 December 2013
                Volume: 9
                Page: 48
                Affiliations
                [1 ]Peking University Sixth Hospital/Institute of Mental Health, Beijing 100191, China
                [2 ]Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China
                [3 ]Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871, China
                Article
                Publisher ID: 1744-9081-9-48
                DOI: 10.1186/1744-9081-9-48
                PMC ID: 3892012
                PubMed ID: 24377651
                SO-VID: 2848876f-fa1d-49a1-b791-c5156d60dbc1
                Copyright © Copyright © 2013 Liu et al.; licensee BioMed Central Ltd.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 September 2013
                Date accepted : 27 December 2013
                Categories
                Subject: Research

                ScienceOpen disciplines: Neurology
                Keywords: attention-deficit/hyperactivity disorder (adhd),baiap2,hemispheric asymmetry,subtype
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: attention-deficit/hyperactivity disorder (adhd), baiap2, hemispheric asymmetry, subtype

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