However, there has been a notable lack of reproducible GWAS findings, which may be attributed to lack of statistical power but also heterogeneity in the disorders. Both disorders have been found to be polygenic in nature, with many common single nucleotide polymorphisms (SNPs) each conferring small risks. īoth ADHD and OCD have been the focus of considerable genetic research, including a small number of genome-wide association studies (GWAS), given their relative heritability estimates of 70–80% and 40–65%, respectively. The estimated prevalence of OCD in childhood and adult populations is similar, approximately 1–3%. These behaviors and thoughts can impair social and occupational functioning in individuals with OCD. ![]() Core features of OCD consist of recurrent and unwanted thoughts, urges, and repetitive behaviors or mental acts performed to reduce anxiety or a sense of dread. ![]() ADHD affects approximately 5% of children and adolescents, and 2.5% of adults. ĪDHD is characterized by inattention, hyperactivity, and impulsivity mostly in childhood but it can persist into adolescence and adulthood. Elucidating the etiologies and pathophysiologies of these disorders has proven challenging as they have historically been classified based on varying clinical profiles, rather than underlying biology. Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders.Īttention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are common, heterogeneous disorders that can co-occur or occur with other neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and Tourette syndrome (TS). Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. ![]() ![]() This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4–18 years) using DNA extracted from saliva. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker.
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