Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Data availability: We have provided summary statistics for the top 10,000 SNPs (Supplementary Data Set). Full GWAS summary statistics for the 23andMe dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. Interested investigators should email dataset-request@23andme.com for more information. GWAS summary statistics for the UKB GWAS of AUDIT scores will be available on request.

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Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNPbased heritability of self-reported alcohol consumption of 13% (se = 0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e. = 0.09, P-value = 7.16 × 10 − 23 ). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG = 0.18, s.e. = 0.03), high-density lipoprotein cholesterol (rG = 0.28, s.e. = 0.05), smoking (rG = 0.40, s.e. = 0.06) and various anthropometric traits (for example, overweight, rG = − 0.19, s.e. = 0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

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Background: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies (GWASs). PGS methods differ in which DNA variants are included and the weights assigned

Background People who opt to participate in scientific studies tend to be healthier, wealthier and more educated than the broader population. Although selection bias does not always pose a problem for analysing the relationships between exposures and diseases or other outcomes, it can lead to biased effect size estimates. Biased estimates may weaken the utility of genetic findings because the goal is often to make inferences in a new sample (such as in polygenic risk score analysis). Methods We used data from UK Biobank, Generation Scotland and Partners Biobank and conducted phenotypic and genome-wide association analyses on two phenotypes that reflected mental health data availability: (i) whether participants were contactable by e-mail for follow-up; and (ii) whether participants responded to follow-up surveys of mental health. Results In UK Biobank, we identified nine genetic loci associated (P <5 × 10–8) with e-mail contact and 25 loci associated with mental health survey completion. Both phenotypes were positively genetically correlated with higher educational attainment and better health and negatively genetically correlated with psychological distress and schizophrenia. One single nucleotide polymorphism association replicated along with the overall direction of effect of all association results. Conclusions Re-contact availability and follow-up participation can act as further genetic filters for data on mental health phenotypes.

A mucocele is an epithelial lined mucus-containing sac completely filling a paranasal sinus and capable of expansion. They are relatively unusual, occurring most frequently in the fronto-ethmoidal region. The imaging features on plain X-ray, computerized tomography and magnetic resonance imaging are relatively characteristic allowing distinction of the lesion from other pathologies in this area although the mucoceles may occur in association with other pathologies such as nasal polyposis and neoplasia.