Case-control study of six genes asymmetrically expressed in the two cerebral hemispheres: association of BAIAP2 with attention-deficit/hyperactivity disorder.
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.
Ribasés
Marta
M
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.
Bosch
Rosa
R
Hervás
Amaia
A
Ramos-Quiroga
Josep Antoni
JA
Sánchez-Mora
Cristina
C
Bielsa
Anna
A
Gastaminza
Xavier
X
Guijarro-Domingo
Sílvia
S
Nogueira
Mariana
M
Gómez-Barros
Núria
N
Kreiker
Susanne
S
Gross-Lesch
Silke
S
Jacob
Christian P
CP
Lesch
Klaus-Peter
KP
Reif
Andreas
A
Johansson
Stefan
S
Plessen
Kerstin J
KJ
Knappskog
Per M
PM
Haavik
Jan
J
Estivill
Xavier
X
Casas
Miguel
M
Bayés
Mònica
M
Cormand
Bru
B
D000328:Adult; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D003431:Cross-Cultural Comparison; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009664:Norway; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013030:Spain
C119539:BAIAP2 protein, human; D009419:Nerve Tissue Proteins