Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.

Polygenic Analyses Show Important Differences Between Major Depressive Disorder Symptoms Measured Using Various Instruments.

Background: Symptoms of major depressive disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire-9 (PHQ-9) (current symptoms) and the Composite International Diagnostic Interview Short-Form (CIDI-SF) (worst-episode symptoms). We performed a systematic comparison between them for their genetic architecture and utility in investigating MDD heterogeneity.

Methods: Using data from the UK Biobank (n = 41,948-109,417), we assessed the single nucleotide polymorphism heritability and genetic correlation (r) of both sets of MDD symptoms.

Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals.

Phenotype integration improves power and preserves specificity in biobank-based genetic studies of major depressive disorder.

Biobanks often contain several phenotypes relevant to diseases such as major depressive disorder (MDD), with partly distinct genetic architectures. Researchers face complex tradeoffs between shallow (large sample size, low specificity/sensitivity) and deep (small sample size, high specificity/sensitivity) phenotypes, and the optimal choices are often unclear. Here we propose to integrate these phenotypes to combine the benefits of each.

Polygenic analyses show important differences between MDD symptoms collected using PHQ9 and CIDI-SF.

Symptoms of Major Depressive Disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire 9 (PHQ9, for current symptoms), and the Composite International Diagnostic Interview Short-Form (CIDI-SF, for lifetime worst-episode symptoms). Using data from the UKBiobank, we show that corresponding symptoms endorsed through PHQ9 and CIDI-SF have low to moderate genetic correlations (rG=0.43-0.

Accuracy of haplotype estimation and whole genome imputation affects complex trait analyses in complex biobanks.

Sample recruitment for research consortia, biobanks, and personal genomics companies span years, necessitating genotyping in batches, using different technologies. As marker content on genotyping arrays varies, integrating such datasets is non-trivial and its impact on haplotype estimation (phasing) and whole genome imputation, necessary steps for complex trait analysis, remains under-evaluated. Using the iPSYCH dataset, comprising 130,438 individuals, genotyped in two stages, on different arrays, we evaluated phasing and imputation performance across multiple phasing methods and data integration protocols.

Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes.

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10.

Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants.

Background: Language plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual's social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the linguistic overlaps across these disorders; investigations into their genetic overlaps are limited.

Genetic predictors of educational attainment and intelligence test performance predict voter turnout.

Although the genetic influence on voter turnout is substantial (typically 40-50%), the underlying mechanisms remain unclear. Across the social sciences, research suggests that 'resources for politics' (as indexed notably by educational attainment and intelligence test performance) constitute a central cluster of factors that predict electoral participation. Educational attainment and intelligence test performance are heritable.

Association between GLP-1 receptor gene polymorphisms with reward learning, anhedonia and depression diagnosis.

Background: Glucagon-like peptide-1 receptors (GLP-1Rs) are widely expressed in the brain. Evidence suggests that they may play a role in reward responses and neuroprotection. However, the association of GLP-1R with anhedonia and depression diagnosis has not been studied.

Shared Molecular Neuropathology Across Major Psychiatric Disorders Parallels Polygenic Overlap.

(Gandal et al., "Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap" Science 09 Feb 2018:Vol. 359, Issue 6376, pp.