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Linkage analysis of attention deficit hyperactivity disorder.

ABSTRACT: Results of behavioral genetic and molecular genetic studies have converged to suggest that both genes contribute to the development of ADHD. Although prior linkage studies have produced intriguing results, their results have been inconsistent, with no clear pattern of results emerging across studies. We genotyped 5,980 SNPs across the genome in 1,187 individuals from families with children diagnosed with ADHD. We then performed two nonparametric linkage analyses on ADHD families: (1) an affected sibling pair linkage analysis on 217 families with 601 siblings diagnosed with ADHD and (2) a variance components linkage analysis using the number of ADHD symptoms as the phenotype on 260 families with 1,100 phenotyped siblings. The affection status linkage analysis had a maximum LOD score of 1.85 on chromosome 8 at 54.2 cM. The maximum LOD score in the variance components linkage analysis was 0.8 on chromosome 8 at 93.4 cM. The absence of regions of significant or suggestive linkage in these data suggest that there are no genes of large effect contributing to the ADHD phenotype.

SUBMITTER: Faraone SV

PROVIDER: S-EPMC4511106 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Linkage analysis of attention deficit hyperactivity disorder.

Faraone Stephen V SV Doyle Alysa E AE Lasky-Su Jessica J Sklar Pamela B PB D'Angelo Eugene E Gonzalez-Heydrich Joseph J Kratochvil Christopher C Mick Eric E Klein Kristy K Rezac Amy J AJ Biederman Joseph J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20081201 8

Results of behavioral genetic and molecular genetic studies have converged to suggest that both genes contribute to the development of ADHD. Although prior linkage studies have produced intriguing results, their results have been inconsistent, with no clear pattern of results emerging across studies. We genotyped 5,980 SNPs across the genome in 1,187 individuals from families with children diagnosed with ADHD. We then performed two nonparametric linkage analyses on ADHD families: (1) an affected ...[more]

PMID: 18081027

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Project description:BackgroundAttention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric condition, but it has been difficult to identify genes underlying this disorder. This study aimed to explore genetics of ADHD in an ethnically homogeneous Norwegian population by means of a genome-wide association (GWA) analysis followed by examination of candidate loci.Materials and methodsParticipants were recruited through Norwegian medical and birth registries as well as the general population. Presence of ADHD was defined according to DSM-IV criteria. Genotyping was performed using Illumina Human OmniExpress-12v1 microarrays. Statistical analyses were divided into several steps: (1) genome-wide association in the form of logistic regression in PLINK and follow-up pathway analyses performed in DAPPLE and INRICH softwares, (2) SNP-heritability calculated using genome-wide complex trait analysis (GCTA) tool, (3) gene-based association tests carried out in JAG software, and (4) evaluation of previously reported genome-wide signals and candidate genes of ADHD.ResultsIn total, 1.358 individuals (478 cases and 880 controls) and 598.384 autosomal SNPs were subjected to GWA analysis. No single polymorphism reached genome-wide significance. The strongest signal was observed at rs9949006 in the ENSG00000263745 gene (OR=1.51, 95% CI 1.28-1.79, p=1.38E-06). Pathway analyses of the top SNPs implicated genes involved in the regulation of gene expression, cell adhesion and inflammation. Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21-1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14-1.66, p=8.31E-04).ConclusionThis study confirms the complexity and heterogeneity of ADHD etiology. Taken together with previous findings, our results point to a spectrum of biological mechanisms underlying the symptoms of ADHD, providing targets for further genetic exploration of this complex disorder.

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Linkage analysis of attention deficit hyperactivity disorder.

Publications

Linkage analysis of attention deficit hyperactivity disorder.

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