Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin
AbstractThe co-occurrence of migraine and glycemic traits has long been reported in observational epidemiological studies, but it has remained unknown how they are linked genetically. We used large-scale GWAS summary statistics on migraine, headache, and nine glycemic traits in European populations to perform cross-trait analyses to estimate genetic correlation, identify shared genomic regions, loci, genes, and pathways, and test for causal relationships. Out of the nine glycemic traits, significant genetic correlation was observed for fasting insulin (FI) and glycated haemoglobin (HbA1c) with both migraine and headache, w...
Source: Human Genetics - February 20, 2023 Category: Genetics & Stem Cells Source Type: research
Rare structural variants, aneuploidies, and mosaicism in individuals with Mullerian aplasia detected by optical genome mapping
AbstractThe molecular basis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome remains largely unknown. Pathogenic variants inWNT4 andHNF1B have been confirmed in a small percent of individuals. A variety of copy number variants have been reported, but causal gene(s) remain to be identified. We hypothesized that rare structural variants (SVs) would be present in some individuals with MRKH, which could explain the genetic basis of the syndrome. Large molecular weight DNA was extracted from lymphoblastoid cells from 87 individuals with MRKH and available parents. Optical genome mapping (OGM) was performed to identify SVs, whi...
Source: Human Genetics - February 17, 2023 Category: Genetics & Stem Cells Source Type: research
Using comprehensive genomic and functional analyses for resolving genotype –phenotype mismatches in children with suspected CMMRD in Lebanon: an IRRDC study
This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges. (Source: Human Genetics)
Source: Human Genetics - February 15, 2023 Category: Genetics & Stem Cells Source Type: research
Beyond IBD: the genetics of other early-onset diarrhoeal disorders
AbstractDiarrhoeal disorders in childhood extend beyond the inflammatory bowel diseases. Persistent and severe forms of diarrhoea can occur from birth and are associated with significant morbidity and mortality. These disorders can affect not only the gastrointestinal tract but frequently have extraintestinal manifestations, immunodeficiencies and endocrinopathies. Genomic analysis has advanced our understanding of these conditions and has revealed precision-based treatment options such as potentially curative haematopoietic stem cell transplant. Although many new mutations have been discovered, there is frequently no clea...
Source: Human Genetics - February 14, 2023 Category: Genetics & Stem Cells Source Type: research
Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia
AbstractPhosphomannomutase 2 (PMM2) deficiency causes Congenital Disorder of Glycosylation (PMM2-CDG), but does not have a recognised association with Inflammatory Bowel Disease (IBD). A distinct clinical syndrome of hyperinsulinism and autosomal recessive polycystic kidney disease (HIPKD) arises in the context of a specific variant in thePMM2 promotor, either in homozygosity, or compound heterozygous with a deleteriousPMM2 variant. Here, we describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6, and 10 years of age. In each case, intestinal inflammation coincided with the unusual ...
Source: Human Genetics - February 11, 2023 Category: Genetics & Stem Cells Source Type: research
Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis
In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health do mains. (Source: Human Genetics)
Source: Human Genetics - February 11, 2023 Category: Genetics & Stem Cells Source Type: research
Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia
AbstractPhosphomannomutase 2 (PMM2) deficiency causes Congenital Disorder of Glycosylation (PMM2-CDG), but does not have a recognised association with Inflammatory Bowel Disease (IBD). A distinct clinical syndrome of hyperinsulinism and autosomal recessive polycystic kidney disease (HIPKD) arises in the context of a specific variant in thePMM2 promotor, either in homozygosity, or compound heterozygous with a deleteriousPMM2 variant. Here, we describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6, and 10 years of age. In each case, intestinal inflammation coincided with the unusual ...
Source: Human Genetics - February 11, 2023 Category: Genetics & Stem Cells Source Type: research
Phenome-wide genetic-correlation analysis and genetically informed causal inference of amyotrophic lateral sclerosis
In conclusion, this phenome-wide investigation of ALS polygenic architecture highlights the widespread pleiotropy linking this disorder with several health do mains. (Source: Human Genetics)
Source: Human Genetics - February 11, 2023 Category: Genetics & Stem Cells Source Type: research
Interpreting variants in genes affected by clonal hematopoiesis in population data
AbstractReference population databases like the Genome Aggregation Database (gnomAD) have improved our ability to interpret the human genome. Variant frequencies and frequency-derived tools (such as depletion scores) have become fundamental to variant interpretation and the assessment of variant –gene–disease relationships. Clonal hematopoiesis (CH) obstructs variant interpretation as somatic variants that provide proliferative advantage will affect variant frequencies, depletion scores, and downstream filtering. Further, default filtering of variants or genes associated with CH risks f ilteringbona fide germline varia...
Source: Human Genetics - February 4, 2023 Category: Genetics & Stem Cells Source Type: research
