ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Ribases M, 201121040458
Citation	Ribases M., Ramos-Quiroga J. A., Sanchez-Mora C., Bosch R., Richarte V., Palomar G., Gastaminza X., Bielsa A., Arcos-Burgos M., Muenke M., Castellanos F. X., Cormand B., Bayes M. and Casas M. (2011) "Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study." Genes Brain Behav, 10(2): 149-57.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	334 cases and 334 controls
Predominant Ethnicity	Caucasian
Population	Spain
Gender	71% were males (n = 237)
Age Group	Adults : 30.2 years (SD = 12.4) for adult patients and 42.3 years (SD = 14.2) for controls

Detail Info

Summary	To replicate the association between LPHN3 and ADHD in adults, they undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P-value= 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P-value= 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan.
Total Sample	334 adult patients with ADHD were recruited at the Department of Psychiatry of the Hospital Universitari Vall d¡¯Hebron of Barcelona (Spain). The control sample, consisting of 334 unrelated adult subjects, was from the same geographic area.
Sample Collection	adult patients with ADHD were recruited at the Department of Psychiatry of the Hospital Universitari Vall d'Hebron of Barcelona (Spain). The control sample was from the same geographic area.
Diagnosis Description	All subjects met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria (65.3% combined type, 31.1% inattentive type and 3.6% hyperactive-impulsive type). Diagnosis was blind to genotype and was based on the Structured Clinical Interview for DSM-IV Axis I and II Disorders (SCID-I and SCID-II) and the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID Part I and II). For more details, please refer to the original article.
Technique	Genomic DNA was isolated either from peripheral blood lymphocytes by the salting-out procedure or using magnetic bead technology with the Chemagic DNA kit or from saliva using the Oragene^TMDNA Self-Collection kit. 48 selected SNPs were evaluated with the automated assay design pipeline at ms.appliedbiosystems.com/snplex/snplexStart.jsp. All SNPs were genotyped using the SNPLEX^TM platform.
Analysis Method	For the single-marker analysis, analyses of Hardy-Weinberg equilibrium (HWE) (P-value< 0.01) in cases and controls separately and comparison of genotype and allele frequencies were performed using the SNPASSOC R package (Gonzalez et al . 2007). Correction for multiple testing was performed on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs of the LPHN3 gene. For the multiple-marker analysis, significance was estimated using 10 000 permutations with the UNPHASED software version 3.0.13 (Dudbridge 2003).
Result Description	Single and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P-value= 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P-value= 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively].

SNPs reported by this study (count: 5)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1868790			allelic P-value=0.017, OR=1.39, genotypic P-value=0.020, OR=1.50 for combined ADHD	associated with combined ADHD, but cannot survive the correc...... associated with combined ADHD, but cannot survive the correction for multiple testing More...	Significant
rs13115125			allelic P-value=0.21, genotypic P-value=0.013, OR=1.93 for inattentive ADHD	associated with inattentive ADHD, but cannot survive the cor...... associated with inattentive ADHD, but cannot survive the correction for multiple testing More...	Significant
rs4860106			allelic P-value=0.27, genotypic P-value=0.021, OR=1.77 for inattentive ADHD	associated with inattentive ADHD, but cannot survive the cor...... associated with inattentive ADHD, but cannot survive the correction for multiple testing More...	Significant
rs2122643			allelic P-value=0.032, OR=1.31 for all ADHD, allelic P-value=0.034, OR=1.32 for combined ADHD; genotypic P-value=0.018, OR=1.45 for all ADHD, genotypic P-value=0.53 for combined ADHD	nominal association with ADHD and associated with combined A...... nominal association with ADHD and associated with combined ADHD, but cannot survive the correction for multiple testing More...	Significant
rs6858066			allelic P-value=0.025, OR=1.32, genotypic P-value=0.0019, OR=1.82 for combined ADHD	associated with combined ADHD, and remained associated after...... associated with combined ADHD, and remained associated after correcting for multiple testing More...	Significant

Genes reported by this study (count: 1)