A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy.

Class 2 HLA and PLA2R1 alleles are exceptionally strong genetic risk factors for membranous nephropathy (MN), leading, through an unknown mechanism, to a targeted autoimmune response. Introgressed archaic haplotypes (introduced from an archaic human genome into the modern human genome) might influence phenotypes through gene dysregulation. Here, we investigated the genomic region surrounding the PLA2R1 gene.

Rare disease gene association discovery from burden analysis of the 100,000 Genomes Project data.

To discover rare disease-gene associations, we developed a gene burden analytical framework and applied it to rare, protein-coding variants from whole genome sequencing of 35,008 cases with rare diseases and their family members recruited to the 100,000 Genomes Project (100KGP). Following triaging of the results, 88 novel associations were identified including 38 with existing experimental evidence. We have published the confirmation of one of these associations, hereditary ataxia with , and independent confirmatory evidence has recently been published for four more.

A missense mutation in associated with defective spermatogenesis and male infertility.

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.

Common Risk Variants in Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.

Introduction: Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at and have identified several non- loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry.

Membranous nephropathy in the UK Biobank.

Background: Despite MN being one of the most common causes of nephrotic syndrome worldwide, its biological and environmental determinants are poorly understood in large-part due to it being a rare disease. Making use of the UK Biobank, a unique resource holding a clinical dataset and stored DNA, serum and urine for ~500,000 participants, this study aims to address this gap in understanding.

Methods: The primary outcome was putative MN as defined by ICD-10 codes occurring in the UK Biobank.