Dataset Information

DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism.

ABSTRACT: One of the three most frequently documented copy number variations associated with autism spectrum disorder (ASD) is a 1q21.1 duplication that encompasses sequences encoding DUF1220 protein domains, the dosage of which we previously implicated in increased human brain size. Further, individuals with ASD frequently display accelerated brain growth and a larger brain size that is also associated with increased symptom severity. Given these findings, we investigated the relationship between DUF1220 copy number and ASD severity, and here show that in individuals with ASD (n = 170), the copy number (dosage) of DUF1220 subtype CON1 is highly variable, ranging from 56 to 88 copies following a Gaussian distribution. More remarkably, in individuals with ASD CON1 copy number is also linearly associated, in a dose-response manner, with increased severity of each of the three primary symptoms of ASD: social deficits (p = 0.021), communicative impairments (p = 0.030), and repetitive behaviors (p = 0.047). These data indicate that DUF1220 protein domain (CON1) dosage has an ASD-wide effect and, as such, is likely to be a key component of a major pathway underlying ASD severity. Finally, these findings, by implicating the dosage of a previously unexamined, copy number polymorphic and brain evolution-related gene coding sequence in ASD severity, provide an important new direction for further research into the genetic factors underlying ASD.

SUBMITTER: Davis JM

PROVIDER: S-EPMC3961203 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism.

Davis Jonathan M JM Searles Veronica B VB Anderson Nathan N Keeney Jonathon J Dumas Laura L Sikela James M JM

PLoS genetics 20140320 3

One of the three most frequently documented copy number variations associated with autism spectrum disorder (ASD) is a 1q21.1 duplication that encompasses sequences encoding DUF1220 protein domains, the dosage of which we previously implicated in increased human brain size. Further, individuals with ASD frequently display accelerated brain growth and a larger brain size that is also associated with increased symptom severity. Given these findings, we investigated the relationship between DUF1220 ...[more]

PMID: 24651471

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Project description:BackgroundMost patients with substance use disorders (SUDs) never receive treatment and SUDs are under-recognized in primary care (PC) where patients can be treated or linked to treatment. Asking PC patients to directly report SUD symptoms on questionnaires might help identify SUDs but to our knowledge, this approach is previously untested.ObjectiveTo describe the prevalence and severity of DSM-5 SUD symptoms reported by PC patients as part of routine care.DesignCross-sectional study using secondary data.ParticipantsA total of 241,265 adult patients who visited one of 25 PC sites in an integrated health system in Washington state and had alcohol, cannabis, or other drug use screening documented in their EHRs (March 2015-July 2018) were included in main analyses if they had a positive screen for high-risk substance use defined as AUDIT-C score 7-12 points, or report of past-year daily cannabis use or any other drug use.Main measuresThe main outcome was number of SUD symptoms based on Diagnostic and Statistical Manual, 5th edition (DSM-5), reported on Symptom Checklists (0-11) for alcohol or other drugs: 2-3 mild; 4-5 moderate; 6-11 severe.ResultsOf screened patients, 16,776 (5.7%) reported high-risk use of alcohol (2.4%), cannabis (3.9%), and/or other drugs (1.7%), and 65.0-69.9% of those completed Symptom Checklists. Of those with high-risk alcohol use, 52.5% (95% CI 50.9-54.0%) reported ≥ 2 symptoms consistent with mild-severe alcohol use disorders. Of those reporting daily cannabis use, 29.8% (28.6-30.9%) reported ≥ 2 symptoms consistent with mild-severe SUDs. Of those reporting any other drug use, 37.5% (35.7-39.3%) reported ≥ 2 symptoms consistent with mild-severe SUDs.Conclusions and relevanceMany PC patients who screened positive for high-risk substance use reported symptoms consistent with DSM-5 SUDs on self-report Symptom Checklists. Use of SUD Symptom Checklists could support PC providers in making SUD diagnoses and initiating discussions of substance use.

Dataset Information

DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism.

Publications

DUF1220 dosage is linearly associated with increasing severity of the three primary symptoms of autism.

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