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Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

Peer-staffed crisis respite services resulted in lowered rates of Medicaid-funded hospitalizations and health expenditures for participants compared with a comparison group. The findings suggest that peer-staffed crisis respites can achieve system-level impacts.

To further our understanding of the genetics of musicality, we explored associations between a polygenic score for self-reported beat synchronization ability (PGSrhythm) and objectively measured rhythm discrimination, as well as other validated music skills and music-related traits. Using family data, we were able to further explore potential pathways of direct genetic, indirect genetic (through passive gene–environment correlation) and confounding effects (such as population structure and assortative mating). In 5648 Swedish twins, we found PGSrhythm to predict not only rhythm discrimination, but also melody and pitch discrimination (betas between 0.11 and 0.16, p < 0.001), as well as other music-related outcomes (p < 0.05). In contrast, PGSrhythm was not associated with control phenotypes not directly related to music. Associations did not deteriorate within families (N = 243), implying that indirect genetic or confounding effects did not inflate PGSrhythm effects. A correlation (r = 0.05, p < 0.001) between musical enrichment of the family childhood environment and individuals' PGSrhythm, suggests gene–environment correlation. We conclude that the PGSrhythm captures individuals' general genetic musical propensity, affecting musical behavior more likely direct than through indirect or confounding effects.

There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environment, and Cognitive Trait (AFFECT) study presents an opportunity to identify and associate the structure of cognition and symptom-level domains across the mood disorder spectrum in a prospective study from a diverse US population.Participants were recruited from the 23andMe, Inc research participant database and through social media; self-reported diagnosis of MD or BD by a medical professional and medication status data were used to enrich for mood-disorder cases. Remote assessments were used to acquire an extensive range of phenotypes, including mood state, transdiagnostic symptom severity, task-based measures of cognition, environmental exposures, personality traits. In this paper we describe the study design, and the demographic and clinical characteristics of the cohort. In addition we report genetic ancestry, SNP heritability, and genetic correlations with other large cohorts of mood disorders.A total of 48,467 participants were enrolled: 14,768 with MD, 9864 with BD, and 23,835 controls. Upon enrollment, 47% of participants with MD and 27% with BD indicated being in an active mood episode. Cases reported early ages of onset (mean = 13.2 and 14.3 years for MD and BD, respectively), and high levels of recurrence (78.6% and 84.9% with >5 episodes), psychotherapy, and psychotropic medication use. SNP heritability on the liability scale for the ascertained MD participants (0.19–0.21) was consistent with the high level of disease severity in this cohort, while BD heritability estimates (0.16–0.22) were comparable to reports in other large scale genomic studies of mood disorders. Genetic correlations between the AFFECT cohort and other large-scale cohorts were high for MD but not for BD. By incorporating transdiagnostic symptom assessments, repeated measures, and genomic data, the AFFECT study represents a unique resource for dissecting the structure of mood disorders across multiple levels of analysis. In addition, the fully remote nature of the study provides valuable insights for future virtual and decentralized clinical trials within mood disorders.