Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

Psoriatic arthritis often develops in patients with psoriasis and can lead to joint deformity, stiffness, dysfunction, and disability. Psoriatic arthritis is a polygenic disease. and the issue of personalizing the prognosis of its development can only be resolved taking into account the variability of plenty genomic loci associated with the development of the disease. The personification of the prognosis of the disease can be solved taking into account the variability of the set of genomic loci with which its development is associated. The review examines genomic polymorphisms associated with the development of psoriatic arthritis not psoriasis, except of HLA polymorphisms. Genome regions containing polymorphisms, allelic variants of which are associated both with the development of psoriatic arthritis and reducing the likelihood of its occurrence, are described. It has been reported that the predisposition to the development of psoriatic arthritis in patients with psoriasis is determined by genes encoding proteins involved in inflammation and bone metabolism.

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease

Adolescent idiopathic scoliosis (AIS) is a lateral spinal curvature >10° with rotation that affects 2–3% of healthy children across populations. AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown. In this study, we performed exome sequencing of affected individuals within 23 multigenerational families, with the hypothesis that the occurrence of rare, low frequency, disease-causing variants will co-occur in distantly related, affected individuals. Bioinformatic filtering of uncommon, potentially damaging variants shared by all sequenced family members revealed 1448 variants in 1160 genes across the 23 families, with 132 genes shared by two or more families. Ten genes were shared by >4 families, and no genes were shared by all. Gene enrichment analysis showed an enrichment of variants in cytoskeletal and extracellular matrix related processes. These data support a model that AIS is a highly polygenic disease, with few variant-containing genes shared between affected individuals across different family lineages. This work presents a novel resource for further exploration in familial AIS genetic research.

PREIMPLANTATION GENETIC TESTING: Preimplantation genetic testing for polygenic disease risk

Since its introduction to clinical practice, preimplantation genetic testing (PGT) has become a standard of care for couples at risk of having children with monogenic disease and for chromosomal aneuploidy to improve outcomes for patients with infertility. The primary objective of PGT is to reduce the risk of miscarriage and genetic disease and to improve the success of infertility treatment with the delivery of a healthy child. Until recently, the application of PGT to more common but complex polygenic disease was not possible, as the genetic contribution to polygenic disease has been difficult to determine, and the concept of embryo selection across multiple genetic loci has been difficult to comprehend. Several achievements, including the ability to obtain accurate, genome-wide genotypes of the human embryo and the development of population-level biobanks, have now made PGT for polygenic disease risk applicable in clinical practice. With the rapid advances in embryonic polygenic risk scoring, diverse considerations beyond technical capability have been introduced.

Preimplantation Genetic Testing for Polygenic Disease Relative Risk Reduction: Evaluation of Genomic Index Performance in 11,883 Adult Sibling Pairs

Preimplantation genetic testing for polygenic disease risk (PGT-P) represents a new tool to aid in embryo selection. Previous studies demonstrated the ability to obtain necessary genotypes in the embryo with accuracy equivalent to in adults. When applied to select adult siblings with known type I diabetes status, a reduction in disease incidence of 45–72% compared to random selection was achieved. This study extends analysis to 11,883 sibling pairs to evaluate clinical utility of embryo selection with PGT-P. Results demonstrate simultaneous relative risk reduction of all diseases tested in parallel, which included diabetes, cancer, and heart disease, and indicate applicability beyond patients with a known family history of disease.

Analysis of polymorphic DNA markers as potential predictors of myocardial infarction taking into account age

Myocardial infarction (MI) is a multifactorial polygenic disease. It develops because of the complex interaction between many environmental and genetic factors. In this investigation, we have studied associations of MI and rs1042034 (gene APOB), rs4420638 (gene APOC1) rs2070424 (gene SOD1) и rs662 (ген PON1) in an ethnically homogeneous group. The material for analysis was DNA samples of patients (365 men) with onset of MI at the age of 30 to 60 years and 292 essentially healthy men of the control group. The study revealed markers of increased risk of MI: SOD1*A/A, for men under 46 years of age (P=0.029, OR=1.96), APOC1*A/G (P=0.03, OR=2.01), for men over 48 years of age, and APOB*C/C (P=0.031OR=1.8).