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Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children.
Behav Brain Funct 2016; 12(1):2BB

Abstract

BACKGROUND

Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population.

METHODS

A cohort of ADHD 290 patients and 340 controls aged 6-18 years were included in a case-control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants.

RESULTS

After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively.

CONCLUSIONS

We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models.

Authors+Show Affiliations

Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. clara.gomez@idcsalud.es. Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. clara.gomez@idcsalud.es.Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. rriveiro@fjd.es. Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. rriveiro@fjd.es.Department of Pediatrics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. victor.soto@idcsalud.es.Department of Pediatrics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. mrodrigomo@fjd.es.Department of Pediatrics, La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain. ptiradorequero@gmail.com.Department of Epidemiology, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. imahillo@fjd.es.Clinical Pharmacology Department, Instituto de Investigación Sanitaria Princesa (IP), Hospital Universitario de la Princesa, C/Diego de Leon 62, 28006, Madrid, Spain. francisco.abad@salud.madrid.org.Department of Psychiatry, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. jjcarballo@fjd.es.Clinical Research, BUC (Biosciences UAM + CSIC) Program, International Campus of Excellence, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain. rafael.dalre@fuam.uam.es.Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. cayuso@fjd.es. Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. cayuso@fjd.es.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26746237

Citation

Gomez-Sanchez, Clara I., et al. "Attention Deficit Hyperactivity Disorder: Genetic Association Study in a Cohort of Spanish Children." Behavioral and Brain Functions : BBF, vol. 12, no. 1, 2016, p. 2.
Gomez-Sanchez CI, Riveiro-Alvarez R, Soto-Insuga V, et al. Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. Behav Brain Funct. 2016;12(1):2.
Gomez-Sanchez, C. I., Riveiro-Alvarez, R., Soto-Insuga, V., Rodrigo, M., Tirado-Requero, P., Mahillo-Fernandez, I., ... Ayuso, C. (2016). Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. Behavioral and Brain Functions : BBF, 12(1), p. 2. doi:10.1186/s12993-015-0084-6.
Gomez-Sanchez CI, et al. Attention Deficit Hyperactivity Disorder: Genetic Association Study in a Cohort of Spanish Children. Behav Brain Funct. 2016 Jan 8;12(1):2. PubMed PMID: 26746237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. AU - Gomez-Sanchez,Clara I, AU - Riveiro-Alvarez,Rosa, AU - Soto-Insuga,Victor, AU - Rodrigo,Maria, AU - Tirado-Requero,Pilar, AU - Mahillo-Fernandez,Ignacio, AU - Abad-Santos,Francisco, AU - Carballo,Juan J, AU - Dal-Ré,Rafael, AU - Ayuso,Carmen, Y1 - 2016/01/08/ PY - 2015/06/18/received PY - 2015/12/02/accepted PY - 2016/1/10/entrez PY - 2016/1/10/pubmed PY - 2016/10/16/medline SP - 2 EP - 2 JF - Behavioral and brain functions : BBF JO - Behav Brain Funct VL - 12 IS - 1 N2 - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population. METHODS: A cohort of ADHD 290 patients and 340 controls aged 6-18 years were included in a case-control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants. RESULTS: After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively. CONCLUSIONS: We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models. SN - 1744-9081 UR - https://www.unboundmedicine.com/medline/citation/26746237/Attention_deficit_hyperactivity_disorder:_genetic_association_study_in_a_cohort_of_Spanish_children_ L2 - https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/s12993-015-0084-6 DB - PRIME DP - Unbound Medicine ER -