Genetic Associations and Epidemiology

Updated pipeline and genetic data confirm genetically supported drug targets succeed more often; Mendelian (OMIM) support replicates prospectively, while GWAS support is weaker unless coding-linked.

GTEx v8 maps expression and splicing QTLs in 49 tissues from 838 donors: cis-eQTLs cover 94.7% of protein-coding genes, and cross-tissue QTL sharing mirrors cell-type composition.

UK Biobank genetics of 38 blood and urine lab tests yields 1,857 independent loci; combining biomarker and disease polygenic scores improves FinnGen prediction of incident renal failure and alcoholic cirrhosis.

A web platform bundling LD-score regression, DEPICT, MetaXcan, SMR, GSMR and fastBAT over uploaded or 1,500-plus public GWAS summary statistics, with precomputed gene, pathway and tissue results.

A meta-analysis of 807,553 people from 23andMe, UK Biobank and PGC finds 102 depression variants. 87 of them replicate in 1,306,354 individuals, and heritability is enriched in prefrontal brain regions.

Meta-analysis of waist-to-hip ratio adjusted for BMI in 694,649 European-ancestry individuals identifies 463 signals in 346 loci, roughly one-third sexually dimorphic and mostly stronger in women.

Genetic correlations across 25 brain disorders (215,683 cases) reveal broad psychiatric common-variant sharing, largely distinct neurological disorders, and migraine as the only significant cross-category link.

Encoding imputed genotype probabilities at 8 bits in BGEN gave compact files, ~240 million probabilities parsed per second and association results near-identical to 20-bit data (UK BiLEVE chromosome 22).

Genome-wide association meta-analysis of 130,664 major depression cases and 330,470 controls identifies 44 independent risk loci enriched in cortical neurons, conserved mammalian regions, splicing networks, and antidepressant targets.

MR-PRESSO detects pleiotropic outlier instruments in summary-level Mendelian randomization; across 82 traits it found pleiotropy in 41% of significant causal estimates, with distortions from −168% to 189%.

Quality-controlled genotypes for 488,377 UK Biobank participants at 805,426 markers, imputed to ~96 million variants, plus ancestry PCs, kinship (30.3% have close relatives enrolled) and HLA calls.

Polygenic scores built 434 ways in Health and Retirement Study (HRS) participants varied widely in variance explained and inter-score correlation; European-derived weights underperformed in non-Hispanic Blacks.