Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases.

Background: Cardiovascular diseases (CVD) are the leading cause of global mortality, yet current treatments benefit only a subset of patients. To identify new potential treatment targets, we conducted the first proteome wide association study (PWAS) for 26 CVDs using plasma proteomics data from the largest cohort to date (53,022 individuals in the UK Biobank Pharma Proteomics Project (UKB-PPP)).

Methods And Results: We calculated single nucleotide polymorphism (SNP)-protein weights using the UKB-PPP dataset and integrated these weights with genome-wide association study (GWAS) summary statistics for 26 CVDs across three categories (16 cardiac, 5 venous, and 5 cerebrovascular diseases) in up to 1,308,460 individuals.

Systematic functional characterization of non-coding regulatory SNPs associated with central obesity.

Central obesity is associated with higher risk of developing a wide range of diseases independent of overall obesity. Genome-wide association studies (GWASs) have identified more than 300 susceptibility loci associated with central obesity. However, the functional understanding of these loci is limited by the fact that most loci are in non-coding regions.

The Causal Relationships Between Gut Microbiota, Brain Volume, and Intelligence: A Two-Step Mendelian Randomization Analysis.

Background: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence.

Methods: We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (N = 18,340) and intelligence (N = 269,867).

Multi-tissue transcriptome-wide association study reveals susceptibility genes and drug targets for insulin resistance-relevant phenotypes.

Aim: Genome-wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)-relevant phenotypes. However, the genes responsible for these associations remain largely unknown. We aim to identify susceptibility genes for IR-relevant phenotypes via a transcriptome-wide association study.

High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes.

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac).