Case-Control Study of Six Genes Asymmetrically Expressed in the Two Cerebral Hemispheres: Association of BAIAP2 with Attention-Deficit/Hyperactivity Disorder

Marta Ribasés, Rosa Bosch, Amaia Hervás, Josep Antoni Ramos-Quiroga, Cristina Sánchez-Mora, Anna Bielsa, Xavier Gastaminza, Sílvia Guijarro-Domingo, Mariana Nogueira, Núria Gómez-Barros, Susanne Kreiker, Silke Groß-Lesch, Christian P. Jacob, Klaus Peter Lesch, Andreas Reif, Stefan Johansson, Kerstin J. Plessen, Per M. Knappskog, Jan Haavik, Xavier P. EstivillMiguel Casas, Mònica Bayés, Bru Cormand

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Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disease that persists into adulthood in at least 30% of patients. There is evidence suggesting that abnormal left-right brain asymmetries in ADHD patients may be involved in a variety of ADHD-related cognitive processes, including sustained attention, working memory, response inhibition and planning. Although mechanisms underlying cerebral lateralization are unknown, left-right cortical asymmetry has been associated with transcriptional asymmetry at embryonic stages and several genes differentially expressed between hemispheres have been identified. Methods: We selected six functional candidate genes showing at least 1.9-fold differential expression between hemispheres (BAIAP2, DAPPER1, LMO4, NEUROD6, ATP2B3, and ID2) and performed a case-control association study in an initial Spanish sample of 587 ADHD patients (270 adults and 317 children) and 587 control subjects. Results: The single- and multiple-marker analysis provided evidence for a contribution of BAIAP2 to adulthood ADHD (p = .0026 and p = .0016, respectively). We thus tested BAIAP2 for replication in two independent adult samples from Germany (639 ADHD patients and 612 control subjects) and Norway (417 ADHD cases and 469 control subjects). While no significant results were observed in the Norwegian sample, we replicated the initial association between BAIAP2 and adulthood ADHD in the German population (p = .0062). Conclusions: Our results support the participation of BAIAP2 in the continuity of ADHD across life span, at least in some of the populations analyzed, and suggest that genetic factors potentially influencing abnormal cerebral lateralization may be involved in this disorder.

Original languageEnglish
Pages (from-to)926-934
Number of pages9
JournalBiological Psychiatry
Volume66
Issue number10
DOIs
Publication statusPublished - 15 Nov 2009
Externally publishedYes

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Keywords

  • ADHD
  • attention-deficit hyperactivity disorder
  • BAIAP2
  • brain asymmetry
  • case-control association study

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Ribasés, M., Bosch, R., Hervás, A., Ramos-Quiroga, J. A., Sánchez-Mora, C., Bielsa, A., Gastaminza, X., Guijarro-Domingo, S., Nogueira, M., Gómez-Barros, N., Kreiker, S., Groß-Lesch, S., Jacob, C. P., Lesch, K. P., Reif, A., Johansson, S., Plessen, K. J., Knappskog, P. M., Haavik, J., ... Cormand, B. (2009). Case-Control Study of Six Genes Asymmetrically Expressed in the Two Cerebral Hemispheres: Association of BAIAP2 with Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 66(10), 926-934. https://doi.org/10.1016/j.biopsych.2009.06.024