Rare and low-frequency coding genetic variants contribute to pediatric-onset multiple sclerosis.

BACKGROUND: Rare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown. OBJECTIVE: To test whether genes harboring rare variants associated with adult-onset MS risk (PRF1, PRKRA, NLRP8, and HDAC7) and 52 major histocompatibility complex (MHC) genes are associated with POMS. METHODS: We analyzed DNA samples from 330 POMS cases and 306 controls from the US Network of Pediatric MS Centers and Kaiser Permanente Northern California for which Illumina ExomeChip genotypes were available. Using the gene-based method "SKAT-O," we tested the association between candidate genes and POMS risk. RESULTS: After correction for multiple comparisons, one adult-onset MS gene (PRF1, p = 2.70 × 10-3) and two MHC genes (BRD2, p = 5.89 × 10-5 and AGER, p = 7.96 × 10-5) were significantly associated with POMS. Results suggest these are independent of HLA-DRB1*1501. CONCLUSION: Findings support a role for rare coding variants in POMS susceptibility. In particular, rare minor alleles within PRF1 were more common among individuals with POMS compared to controls while the opposite was true for rare variants within significant MHC genes, BRD2 and AGER. These genes would not have been identified by common variant studies, emphasizing the merits of investigating rare genetic variation in complex diseases.

Sociodemographic Associations With Blood Pressure in 10-14-Year-Old Adolescents.

PURPOSE: To determine the association between sociodemographic characteristics and blood pressure among a demographically diverse population-based sample of 10-14-year-old US adolescents. METHODS: We conducted cross-sectional analyses of data from the Adolescent Brain Cognitive Development Study (N = 4,466), year two (2018-2020). Logistic and linear regression models were used to determine the association between sociodemographic characteristics (sex, race/ethnicity, sexual orientation, household income, and parental education) with blood pressure among early adolescents. RESULTS: The sample was 49.3% female and 46.7% non-White. Overall, 4.1% had blood pressures in the hypertensive range. Male sex was associated with 48% higher odds of hypertensive-range blood pressures than female sex (95% confidence interval [CI], 1.02; 2.14), and Black race was associated with 85% higher odds of hypertensive-range blood pressures compared to White race (95% CI, 1.11; 3.08). Several annual household income categories less than $100,000 were associated with higher odds of hypertensive-range blood pressures compared to an annual household income greater than $200,000. We found effect modification by household income for Black adolescents; Black race (compared to White race) was more strongly associated with higher odds of hypertensive-range blood pressures in households with income greater than $75,000 (odds ratio 3.92; 95% CI, 1.95; 7.88) compared to those with income less than $75,000 (odds ratio 1.53; 95% CI, 0.80; 2.92). DISCUSSION: Sociodemographic characteristics are differentially associated with higher blood pressure in early adolescents. Future research could examine potential mediating factors (e.g., physical activity, nutrition, tobacco) linking sociodemographic characteristics and blood pressure to inform targeted interventions.

Social epidemiology of online dating in U.S. early adolescents.

OBJECTIVE: To investigate the prevalence and sociodemographic associations of online dating in a demographically diverse U.S. national cohort of early adolescents. METHODS: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020, ages 11-12; N = 10,157). Multivariable logistic regression analyses were employed to estimate associations between sociodemographic factors (e.g., age, sex, race/ethnicity, sexual orientation, household income, parental education) and early adolescent-reported online dating behaviors. RESULTS: Overall, 0.4% (n = 38) of participants reported ever using a dating app. Males (AOR 2.72, 95% CI 1.11-6.78) had higher odds of online dating compared to females, and sexual minority identification (e.g., lesbian, gay, or bisexual; AOR 12.97, 95% CI 4.32-38.96) was associated with greater odds of online dating compared to heterosexual identification. CONCLUSION: Given the occurrence of online dating among early adolescents despite age restrictions, interventions might address age misrepresentation. Adolescent sexual health education may consider incorporating anticipatory guidance on online dating, especially for males and sexual minorities. Future research could further investigate online dating patterns from early to late adolescence and associated health effects.