Nature Human Behaviour

BackgroundEvidence from observational studies suggests an association between mental disorders and cancers. However, the causality of this association remains unclear. MethodsWe collected genome-wide association study (GWAS) summary statistics of five mental disorders from the Psychiatric Genomics Consortium (PGC, 72,517 to 500,199 participants), paired with GWAS summary statistics of the risks of 18 cancer types from the UK Biobank (167,020 to 361,194 participants) and FinnGen database (110,52...

Depression is one of the most prevalent psychiatric disorders and is one of the leading causes of health ailment worldwide. It is known to be highly heritable and is frequently comorbid with other mental and physical traits. This observation motivated us to look deeper into the genetic and phenotypic connections between depression and other traits in order to identify correlations as well as potentially causal connections between them. In this study, we analyzed data from the UK biobank to syste...

Depression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Previous studies have revealed substantial genetic overlap between depression, anxiety, and a closely related personality trait - neuroticism. Here, we use factor analysis and genomic structural equation modelling (Genomic SEM) to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism. Symptoms of depression and anxiety loaded o...

Large biobank samples provide an opportunity to integrate broad phenotyping, familial records, and molecular genetics data to study complex traits and diseases. We introduce Pearson-Aitken Family Genetic Risk Scores (PA-FGRS), a new method for estimating disease liability from patterns of diagnoses in extended, age-censored genealogical records. We then apply the method to study a paradigmatic complex disorder, Major Depressive Disorder (MDD), using the iPSYCH2015 case-cohort study of 30,949 MDD...

While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited. To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We harnessed the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via ...

BackgroundThe genetic role of blood lipids (BL) in the shared genetic etiology between major depressive disorder (MDD) and myocardial infarction (MI) has not been fully characterized. MethodsWe first evaluated genetic associations and causal inferences between MDD, MI and the quantitative traits of BL. To further unravel the underlying genetic mechanisms, we performed multi-trait association analysis to identify novel or pleiotropic genomic risk loci, and shared causal variants for diseases inv...

BackgroundDuring the first year of the COVID-19 pandemic, the most effective way to reduce transmission and to protect oneself was to reduce contact with others. However, it is unclear how behavior changed, despite numerous surveys about peoples attitudes and actions during the pandemic and public health efforts to influence behavior. MethodsWe used two sources of data to quantify changes in behavior at the county level during the first year of the pandemic in the United States: aggregated mobi...

We introduce LDAK-PBAT, a novel tool for detecting gene pathways associated with complex traits. LDAK-PBAT tests pathways for significance using a heritability-based framework that controls for both the contributions of genes not in the pathway and of inter-genic SNPs. LDAK-PBAT is computationally efficient, requiring only GWAS summary statistics and a reference panel, and when applied to human traits, can test 1000s of pathways within minutes. When assessed using simulated phenotypes, we find ...

Polygenic prediction has yet to make a major clinical breakthrough in precision medicine and psychiatry, where the application of polygenic risk scores are expected to improve clinical decision-making. Most widely used approaches for estimating polygenic risk scores are based on summary statistics from external large-scale genome-wide association studies, which relies on assumptions of matching data distributions. This may hinder the impact of polygenic risk scores in modern diverse populations ...

BackgroundIn response to the coronavirus pandemic, social distancing became a widely deployed countermeasure in March 2020. We examined whether healthier and wealthier places more successfully implemented social distancing. MethodsMobile device location data were used to quantify declines in movement by county (n=2,633) in the United States of America, comparing April 15-17 (n=65,544,268 traces) to baseline of February 17 - March 7. Negative binomial regression was used to estimate gradients of...

Cross-trait analyses are a powerful approach for refining our understanding of the genetic architectures underlying complex traits. Although many cross-trait association methods exist, a systematic evaluation of their performance is lacking. We compare true and false positive rates of several other methods using numerical (up to 300 traits) and genotype (up to 4 traits) simulations and introduce a new cross-trait association method, SumRank. For two traits, ConjFDR, SumRank, and GPA showed high ...

BackgroundWhile COVID-19 outcomes are associated with increased anxiety, individuals affected by anxiety disorders are more likely to develop severe COVID-19 outcomes. MethodsWe used genome-wide data from UK Biobank (up to 420,531 participants), FinnGen Project (up to 329,077 participants), Million Veteran Program (175,163 participants), and COVID-19 Host Genetics Initiative (up to 122,616 cases and 2,475,240 controls) to investigate possible causal effects and shared genetic mechanisms linking...

We conducted the largest genome-wide meta-analysis of borderline personality disorder (BPD) to date, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci, and nine risk genes in the gene-based analysis. We observed a single-nucleotide polymorphism (SNP) heritability of 17.3% and derived polygenic scores (PGS) predicted 4.6% of the phen...

Investigating the genetic heterogeneity of psychiatric disorders, such as Major Depressive Disorder (MDD) is a key area of research, aimed at increasing etiological insights and ultimately improving clinical outcomes via personalized treatment. Heterogeneity is typically investigated by analyzing disorder subtypes (e.g. depression with/without comorbid anxiety), where heritabilities of the genome-wide association study (GWAS) of each subtype versus controls are estimated, followed by estimation ...

The US public health system is organized in 3 levels: national, state-level, and county-level. Public health messaging both within and across these scales may not always be consistent, and for transmissible public health threats where cases in one spatial location may impact other areas, this lack of consistency could create problems. Here, we collected and analyzed data on influenza vaccination recommendations across public health administration levels. We assess spatial heterogeneity at the co...

During the COVID-19 epidemic, many health professionals started using mass communication on social media to relay critical information and persuade individuals to adopt preventative health behaviors. Our group of clinicians and nurses developed and recorded short video messages to encourage viewers to stay home for the Thanksgiving and Christmas Holidays. We then conducted a two-stage clustered randomized controlled trial in 820 counties (covering 13 States) in the United States of a large-scale...

Post-traumatic Stress Disorder (PTSD) is a common debilitating mental disorder, that occurs in some individuals following extremely traumatic events. Traditional identification of Genetic Markers (GM) for PTSD is mainly based on a statistical clinical approach by comparing PTSD patients with normal controls. However, these statistical studies present limitations, often generating inconsistent results. Few studies have yet examined thoroughly the role of somatic mutations, PTSD disease pathways a...

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n=2633) completing the C-19 Covid symptom tracker app allowed classical twin studies of covid-19 symptoms including predicted covid-19, a symptom-based algorithm predicting true infection derived in app users tested for SARS-CoV-2. We found heritability for fever = 41 (95% confidence intervals 12-70)%; anosmia 47 (27-67)%; delirium 49 (24-75)%; and predicted covid-19 gave heritability = 50 (29-...

Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic risk factors across mental health traits. However, mental health is genetically correlated with socio-economic status (SES) and it is therefore important to investigate and disentangle the genetic relationship between mental health and SES....

Genomics has been forecasted to revolutionise human health by improving medical treatment through a better understanding of the molecular mechanisms of human diseases. Despite great successes of the last decades genome-wide association studies (GWAS), the results have to a limited extent been translated to genomic medicine. We propose, that one route to get closer to improved medical treatment is by understanding the genetics of medication-use. Here we obtained entire medication profiles from 33...