Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups.

Prediction and Characterization of Genetically Regulated Expression of Target Tissues in Asthma.

Background: Genetic control of gene expression in asthma-related tissues is not well-characterized, particularly for African-ancestry populations, limiting advancement in our understanding of the increased prevalence and severity of asthma in those populations.

Objective: To create novel transcriptome prediction models for asthma tissues (nasal epithelium and CD4+ T cells) and apply them in transcriptome-wide association study (TWAS) to discover candidate asthma genes.

Methods: We developed and validated gene expression prediction databases for unstimulated CD4+ T cells (CD4+T) and nasal epithelium using an elastic net framework.

Predictive genetic panel for adult asthma using machine learning methods.

Background: Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis.

Objective: We sought to develop a predictive genetic panel for asthma using machine learning methods.

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

Background: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry.

Methods: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype.

Lipid mediators are detectable in the nasal epithelium and differ by asthma status in female subjects.

Background: Lipid mediators, bioactive products of polyunsaturated fatty acid metabolism, contribute to inflammation initiation and resolution in allergic diseases; however, their presence in lung-related biosamples has not been fully described.

Objective: We aimed to quantify lipid mediators in the nasal airway epithelium and characterize preliminary associations with asthma.

Methods: Using liquid chromatography-mass spectrometry, we conducted a pilot study to quantify 56 lipid mediators from nasal epithelial samples collected from 11 female participants of an outpatient asthma clinic and community controls (aged 30-55 years).

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum.

Background: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+).

Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

In the version of this article initially published, the statement "there are no pan-genomes for any other animal or plant species" was incorrect. The statement has been corrected to "there are no reported pan-genomes for any other animal species, to our knowledge." We thank David Edwards for bringing this error to our attention.

Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs).

Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts.

Background: COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes.