A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex.

2022

1284-1292

09/2022

1546-1718

The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how combinations of genetic factors determine risk is unclear. In a large family sample, we show that genetic loads of rare and polygenic risk are inversely correlated in cases and greater in females than in males, consistent with a liability threshold that differs by sex. De novo mutations (DNMs), rare inherited variants and polygenic scores were associated with various dimensions of symptom severity in children and parents. Parental age effects on risk for ASD in offspring were attributable to a combination of genetic mechanisms, including DNMs that accumulate in the paternal germline and inherited risk that influences behavior in parents. Genes implicated by rare variants were enriched in excitatory and inhibitory neurons compared with genes implicated by common variants. Our results suggest that a phenotypic spectrum of ASD is attributable to a spectrum of genetic factors that impact different neurodevelopmental processes.

10.1038/s41588-022-01064-5

Nat Genet

35654974

Reduced Socioeconomic Disparities in Cleft Care After Implementing a Cleft Nurse Navigator Program.

2021

10556656211005646

2021 Apr 07

1545-1569

<p><strong>OBJECTIVE: </strong>To evaluate the impact of a Cleft Nurse Navigator (CNN) program on care for patients with cleft lip and cleft palate and assess the programs efficacy to reduce existing socioeconomic disparities in care.</p>

<p><strong>DESIGN: </strong>Retrospective review and outcomes analysis (n = 739).</p>

<p><strong>SETTING: </strong>Academic tertiary care center.</p>

<p><strong>PATIENTS: </strong>All patients presenting with cleft lip and/or cleft palate (CL/P) born between May 2009 and November 2019 with exclusions for atypical clefts, submucous cleft palates, international adoption, and very late presentation (after 250 days of life).</p>

<p><strong>INTERVENTIONS: </strong>Multidisciplinary care coordination program facilitated by the CNN.</p>

<p><strong>MAIN OUTCOME MEASURES: </strong>Patient age at first outpatient appointment and age at surgery, reported feeding issues, weight gain, and patient-cleft team communications.</p>

<p><strong>RESULTS: </strong>After CNN implementation, median age at outpatient appointment decreased from 20 to 16 days ( = .021), volume of patient-cleft team communications increased from 1.5 to 2.8 ( &lt; .001), and frequency of reported feeding concerns decreased (50% to 35%; &lt; .001). In the pre-CNN cohort, nonwhite and publicly insured patients experienced delays in first outpatient appointment ( &lt; .001), cleft lip repair ( &lt; .011), and cleft palate repair ( &lt; .019) compared to white and privately insured patients, respectively. In the post-CNN cohort, there were no significant differences in first appointment timing by race nor surgical timing on the basis of racial identity nor insurance type.</p>

<p><strong>CONCLUSIONS: </strong>A variety of factors lead to delays in cleft care for marginalized patient populations. These findings suggest that a CNN can reduce disparities of access and communication and improve early feeding in at-risk cohorts.</p>

10.1177/10556656211005646

Cleft Palate Craniofac J

33823655

Disparities in Childhood ADHD Symptom Severity by Neighborhood Poverty.

2020

2020 Feb 17

1876-2867

<p><strong>OBJECTIVE: </strong>To determine the association between neighborhood poverty and ADHD severity among children in a large metropolitan area.</p>

<p><strong>METHODS: </strong>This is a secondary analysis of data collected April 2016 to July 2017 at the Children's Hospital of Philadelphia Care Network. We attributed 2015 American Community Survey census tract poverty, defined as percent of individuals with income below poverty level, to each child's residential address. Tracts were grouped from low to high poverty. ADHD severity was determined by Vanderbilt Parent Rating Scale (VPRS) symptom score. We also recorded parent-reported child ADHD medication use.</p>

<p><strong>RESULTS: </strong>A total of 286 children were linked to 203 unique census tracts. The majority of children from high poverty tracts were black and from disadvantaged households. Higher neighborhood poverty was associated with higher VPRS scores and decreased medication use in bivariate analysis. Poverty was no longer associated with VPRS scores in multivariate analysis, but medication use still had a significant negative association with VPRS score. Post-hoc stratification by medication use revealed that neighborhood poverty and VPRS score were significantly associated for children on medication, but not for those off medication.</p>

<p><strong>CONCLUSIONS: </strong>Neighborhood poverty was not associated with ADHD severity in multivariate analysis. This suggests other factors, including medication use, confound the relationship between neighborhood poverty and ADHD severity. Lack of medication treatment was significantly associated with higher symptom burdens for children with access to primary care. Decreased medication use in higher poverty communities warrants exploration and public health interventions to ensure adequate ADHD management for all children.</p>

10.1016/j.acap.2020.02.015

Acad Pediatr

32081765