Diversity in Human Genetics

Analyses of whole-genome and RNA sequencing data from 2,733 African American, Puerto Rican and Mexican American individuals reveal ancestry-specific patterns in the genetic architecture of whole-blood gene expression.

Current ontologies of race, ethnicity and genetic ancestry rely on categorization, but have limitations — as exemplified by multiracial individuals. We argue that including these individuals will foster inclusion by better capturing complex identities, with equity benefits for the full human population.

Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.

MEGAnE is a new tool to detect and genotype mobile element variants (MEVs) from short-read whole-genome sequencing datasets. Genetic analyses implicate MEVs as population-specific drivers of gene expression variation and disease risk.

Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

Here, the authors perform a genome-wide association study for recurrent pregnancy loss without apparent clinical causes and identify a protective HLA haplotype. They also show that rare predicted loss-of-function variants in CDH11 are associated with risk of recurrent pregnancy loss.

Rates of Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) continue to rise in Hispanics and Latinos. Authors developed a digital PCR assay to quantify activation-induced cytidine deaminase activity at risk loci involved in cancer etiology that may contribute to this health disparity.

Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population.

Innovative pharmacogenomic approaches (genetic variation related to medication response) are needed to reduce disease and disparities in Indigenous communities. We support community-based pharmacogenomics research, inclusive of Indigenous values and priorities, to improve the health and well-being of Indigenous peoples.

Most genetic studies for prostate cancer have been performed outside the context of Sub-Saharan Africa. Here, the authors interrogate 247,780 exomic variants for 798 Black South African men and identify genes associated with aggressive disease.

Whole genome sequencing has enabled new insights into the genetic architecture of complex traits, especially through access to low-frequency and rare variation. This Comment highlights the key contributions from this technology and discusses considerations for its use and future perspectives.

Arabs account for 5% of the world population and have a high burden of cardiometabolic disease. Here, the authors optimize polygenic scores for 10 cardiometabolic traits in 5399 Arabs, achieving a performance on par with that among European-ancestry individuals.

Most genetic studies have been done on European cohorts, which affects the efficacy of polygenic risk scores in non-European populations. Here, the authors demonstrate that a colorectal cancer PRS including Asian and European ancestries has improved performance over the European-centric PRS across racial and ethnic groups.

There have been few genome-wide association studies that analyze multiple lipid traits simultaneously, especially in individuals of African ancestry. To address this, the authors performed a multi-trait analysis of GWAS along with fine-mapping to find new genetic loci associated with lipid traits in individuals of African ancestry.

Most genetic studies of disease have been done in European ancestry cohorts, and the relevance to other populations is not guaranteed. Here, the authors use data from 22,000 British South Asian individuals and find that the transferability of polygenic scores was high for lipids and blood pressure, and lower for BMI and coronary artery disease.

Here, the authors use paleogenomic data from the indigenous people of the Canary Islands to shed light on the Prehistory of North Africa, and on how insularity and resources availability shaped the genetic composition of this isolated population.

A genome-wide association study on knee extension strength in 3452 persons of Japanese ancestry 60 years old and above identifies a significant association at a single locus that includes TACC2, a gene encoding a cytoskeleton-related protein.

GWAS meta-analysis associates 12 sequence variants with essential tremor, identifies seven candidate causal genes including CA3 with multiomics-based analysis, and reveals key roles of dopaminergic and GABAergic neurons in the pathogenesis.

A genome-wide association study in the China Kadoorie Biobank identified four novel loci related to snoring, and highlights the relevance of cardiometabolic health to snoring prevention.

A comparison of the frequency of pathogenic mutations in 73 genes in the All of Us cohort highlights the differences in pathogenic variation attributed to ancestry.

A GWAS in a multi-ethnic cohort identifies a novel association between the GLI3 SNP rs2058019 and retinopathy of prematurity (ROP) severity, which was confirmed as relevant to preretinal neovascular disease and human ocular gene expression.

A large multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma, providing insight into the genetic basis of these serious forms of cancer.

A genome-wide association study and fully automatic landmarking approach on frontal 2D face photographs of >6000 Latin Americans identifies novel genomic regions influencing facial features and implicates Neanderthal introgression in nasal shape.

A genome-wide association study for five cognitive phenotypes in a rural South African community suggests several variants associated with general cognition and domain-specific cognitive pathways in this cohort.

A review of citation rates from genomic studies in the GWAS Catalog suggests that sharing summary statistics results, on average, in ~81.8% more citations, highlighting a benefit of publicly sharing GWAS summary statistics.

A genome-wide association study using summary statistics from the UK Biobank identifies ancestry-specific variants associated with pulmonary function among European and African ancestry cohorts.

A multi-ethnic meta-analysis of exome array data from over 27,000 participants identifies several rare variants that could contribute to risk of ocular refractive error.

A phenome-wide association study and polygenic risk score analysis identifies several loci linked to metabolic disease and type 2 diabetes in the Taiwanese population.

A genome-wide association study identifies MFGE8 as protective against coronary atherosclerosis in European and East Asian populations.

Whole-exome sequencing for 51 families in Ghana reveals 7 candidate genes associated with hearing impairment, 6 of which have previously been demonstrated to be expressed in the mouse inner ear.

Despite recent advances in genotyping technologies, cohorts outside of European ancestries are still underrepresented in genome-wide association studies (GWASs). We recognize the scientific imperative of improving diversity in human genomics, and outline the steps we will take as a journal to empower research involving these underrepresented cohorts.