Genome-wide association studies articles from across Nature Portfolio

Whole-genome sequencing data of individuals from the UK Biobank and Iceland and a somatic mutation barcoding strategy enabled detection of clonal hematopoiesis at scale. This comprehensive study provides insights into the epidemiology, somatic and germline genetics, and disease associations of clonal hematopoiesis.

The authors propose “HEELS”, a new method for precise local heritability estimation. It significantly reduces the variances of summary-statistics-based heritability estimators, offering an REML-like estimator without requiring individual-level data.

A downsampling approach to assess causal variant fine-mapping, replication failure rate, finds that commonly used methods may be miscalibrated. Simulations suggest this is probably due to a nonsparse genetic architecture model misspecification. Incorporating infinitesimal effects in the SuSiE and FINEMAP frameworks improves performance.

Cross-ancestry genome-wide association meta-analyses identify new risk loci for peptic ulcer diseases and provide evidence that gastrointestinal cell differentiation and hormone regulation contribute to their etiology.

Genome-wide analyses yield insights into the polygenic effects contributing to clinical heterogeneity in attention deficit hyperactivity disorder, advancing understanding of its genetic etiology and serving as a model for future studies in other complex disorders.

Avery et al. utilize data from the UK Biobank in a multivariable Mendelian randomization study to evaluate the effects of branched chain amino acids (BCAAs) on human disease. Their findings suggest observational studies of BCAA phenotypic effects are prone to substantial error, potentially misleading efforts to develop novel therapeutics.

Evaluation of 17 published functional weighting methods for improving GWAS statistical power demonstrates a tradeoff between high sensitivity and high positive predictive value.

Whole-genome sequencing data of individuals from the UK Biobank and Iceland and a somatic mutation barcoding strategy enabled detection of clonal hematopoiesis at scale. This comprehensive study provides insights into the epidemiology, somatic and germline genetics, and disease associations of clonal hematopoiesis.

Three papers in Nature report on the largest open-access plasma proteomics dataset to date, a valuable resource for understanding human disease and the identification of drug targets.

A paper in Nature finds that nuclear genetic variation can influence heteroplasmy and the human mitochondrial genome.