Sekar Kathiresan

Inferring compound heterozygosity from large-scale exome sequencing data

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

Lipid nanoparticles incorporating a GalNAc ligand enable in vivo liver ANGPTL3 editing in wild-type and somatic LDLR knockout non-human primates

This study develops GalNAc-LNPs for liver gene editing in NHPs, achieving high editing efficiency and ANGPTL3 reduction in both HoFH and wild-type models.

Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases

The paper uses polygenic scores to identify plasma proteins causally linked to cardiometabolic diseases and finds some are targets for existing therapies.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

A coronary artery disease GWAS of 181,522 cases among 1,165,690 participants yields 241 associations (54 new); an eight-predictor consensus nominates 185 candidate causal genes, 94 with ≥3 predictors.

Prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test

This study compares genome sequencing with standard-of-care genetic testing, finding similar diagnostic yields but longer turnaround times for genome sequencing.

South Asian patient population genetics reveal strong founder effects and high rates of homozygosity - new resources for precision medicine

The paper characterizes the genetic structure of South Asian populations, identifies founder effects and high homozygosity, and develops a custom SNP array for genetic studies in the region.

Heterozygous ATP-binding Cassette Transporter G5 Gene Deficiency and Risk of Coronary Artery Disease

This study investigates the impact of heterozygous ABCG5 LoF variants on LDL-C levels and CAD risk, finding a significant association with elevated LDL-C and doubled CAD risk.

Polygenic background modifies penetrance of monogenic variants conferring risk for coronary artery disease, breast cancer, or colorectal cancer

The paper examines how polygenic risk modifies the penetrance of monogenic variants in coronary artery disease, breast cancer, and colorectal cancer across multiple cohorts.

Non-parametric polygenic risk prediction using partitioned GWAS summary statistics

This paper introduces a non-parametric polygenic risk prediction method using GWAS summary statistics, improving prediction accuracy for several diseases.

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

The paper identifies a missense variant in the MARC1 gene associated with protection against cirrhosis and lower liver enzyme and cholesterol levels.

Analysis of cardiac magnetic resonance imaging traits in 29,000 individuals reveals shared genetic basis with dilated cardiomyopathy

This study identifies 26 novel genetic loci associated with cardiac structure and function using MRI data from 29,041 individuals and links them to dilated cardiomyopathy risk.

Low coverage whole genome sequencing enables accurate assessment of common variants and calculation of genome-wide polygenic scores

This study shows low coverage whole genome sequencing can accurately assess common variants and calculate polygenic scores, comparable to genotyping arrays.

Genetic predisposition to myeloproliferative neoplasms implicates hematopoietic stem cell biology

This study identifies 14 genome-wide significant loci and a polygenic signature for myeloproliferative neoplasms, implicating hematopoietic stem cell function and self-renewal in disease risk.

Loss-of-function genomic variants with impact on liver-related blood traits highlight potential therapeutic targets for cardiovascular disease

The paper identifies loss-of-function variants affecting liver-related blood traits that reduce CVD risk without increasing metabolic disease risk, highlighting potential therapeutic targets.

Biological and clinical insights from genetics of insomnia symptoms

The paper identifies 57 genomic regions associated with insomnia symptoms, linking them to phototransduction, ubiquitination, and potential causal relationships with coronary heart disease and depression.

EDEM3 modulates plasma triglyceride level through its regulation of LRP1 expression

The paper identifies a missense variant in EDEM3 associated with lower blood triglyceride levels and shows EDEM3 deficiency increases LRP1 expression, reducing plasma TG through enhanced lipoprotein uptake.

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals

The paper analyzes whole genome sequences from 16,324 individuals to identify genetic variants associated with blood lipid levels and develops a polygenic score for LDL-C.

Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease

A genome-wide polygenic score identifies individuals with a 4-fold increased risk for coronary disease, similar to a rare monogenic mutation.

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

The paper uses whole genome sequencing to identify genetic variants associated with plasma lipoprotein(a) levels and finds high heritability and inter-ethnic differences in Lp(a) risk.

Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum

The paper investigates the impact of rare protein truncating variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals, finding increased risk for several disorders and associations with other phenotypes.

Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

This study uses genome sequencing and epigenomic data to identify genetic variants influencing blood cell traits and uncover regulatory mechanisms in hematopoiesis.

Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

This study finds that ultra-rare disruptive variants in highly constrained genes are associated with reduced educational attainment in the general population.

Human knockouts in a cohort with a high rate of consanguinity

The paper identifies homozygous null mutations in 961 genes in a consanguineous Pakistani cohort and reports their phenotypic consequences.

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

This paper introduces LDpred, a method that improves polygenic risk score accuracy by modeling linkage disequilibrium, showing increased R2 values in schizophrenia and multiple sclerosis datasets.