Dataset Information

Genome-wide association study of conduct disorder symptomatology.

ABSTRACT: Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 × 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder.

SUBMITTER: Dick DM

PROVIDER: S-EPMC3580835 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Genome-wide association study of conduct disorder symptomatology.

Dick D M DM Aliev F F Krueger R F RF Edwards A A Agrawal A A Lynskey M M Lin P P Schuckit M M Hesselbrock V V Nurnberger J J Almasy L L Porjesz B B Edenberg H J HJ Bucholz K K Kramer J J Kuperman S S Bierut L L

Molecular psychiatry 20100629 8

Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were ...[more]

PMID: 20585324

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Project description:Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual's quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value?=?4.7?×?10-7) and DAZ associated protein 2 (DAZAP2, p-value?=?3.13?×?10-8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value?=?5.16?×?10-6), SLC29A2 (p-value?=?6.15?×?10-6) and AKT1 (p-value?=?4.47?×?10-6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.

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Genome-wide association study of conduct disorder symptomatology.

Publications

Genome-wide association study of conduct disorder symptomatology.

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