GWAS in allergy is a study of a meta-analysis of

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different individuals to see if any variant is associated with a trait. GWA s ...

in which

allergy Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

is associated with different susceptibility loci . The three allergic phenotypes studied were to cat,

dust mites House dust mites (HDM, or simply dust mites) are various species of acariform mites belonging to the family Pyroglyphidae that are found in association with dust in dwellings. They are known for causing allergies. Biology Species The curren ...

and pollen, for which found patients presenting allergic symptoms.

History

Allergy is a very common disease and leads to numerous health problems, with allergies and

allergic asthma Asthma is a common chronic (medicine), long-term inflammation, inflammatory disease of the bronchiole, airways of the lungs. It is characterized by variable and recurring symptoms, reversible Airway obstruction, airflow obstruction, and easi ...

are the two most common diseases in the industrialized world, where half of the population of United States tested positive in a test of awareness for at least one common allergen. It has been shown that this type of disease has risen in prevalence over the past ten years. Furthermore, is estimated that

has a hereditary component, suggesting that knowledge of the genetic component is a key to understand the disease. It has been shown that the genes involved in allergy and asthma, are implicated in both immune and inflammatory processes . These genes belong to the family of Toll receptors ( LTRs ) type, a family of proteins that form part of the innate immune system . These receptors are transmembrane and recognize molecular patterns expressed by a wide spectrum of infectious agents, thereby stimulating inflammatory responses, as well as being a link between innate and adaptive immunity . Apart from these receptors, associated with allergy genes encoding

cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

and other

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

occur.

Genome-wide association study

For the study of the relationships between loci and cat allergy, dust mites and

pollen Pollen is a powdery substance produced by most types of flowers of seed plants for the purpose of sexual reproduction. It consists of pollen grains (highly reduced Gametophyte#Heterospory, microgametophytes), which produce male gametes (sperm ...

, questionnaires and

23andMe 23andMe Holding Co. is an American personal genomics and biotechnology company based in South San Francisco, California. It is best known for providing a direct-to-consumer genetic testing service in which customers provide a saliva testing, sali ...

ALSPAC mothers association were performed . They have conducted numerous studies of genome-wide association (GWA) which are an analysis of

genetic variation Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources ...

across the entire

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as the DNA within each of the 23 distinct chromosomes in the cell nucleus. A small DNA molecule is found within individual Mitochondrial DNA, mitochondria. These ar ...

in order to identify their association to an observable trait. In this case the association being studied is a polymorphism between

SNPs In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

or single nucleotide and allergy. Thus it can be concluded that the appearance of one or several SNPs or deletion appears in a disease phenotype. GWA studies for allergies shared effects were performed, and 22 loci were identified with a significant association to allergy symptoms and other immune-related phenotypes or asthma in previous GWA studies, being therefore a meta-analysis. Furthermore, it has been found to evidence a single locus specific allergy on chromosome 6, namely in a region of the

major histocompatibility complex The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...

(MHC), clearly associating with cat allergy effects.

EQTL study

The eQTL analysis determines loci associated with a quantitative trait, where expression studies of loci associated with traits such as allergy are performed, with a functional explanation . Through these studies, an overlap between loci associated with allergy was observed and it loci previously implicated in autoimmune diseases. Thus, in a region of

chromosome 5 Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 182 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. Ch ...

, presents a loci associated with allergic asthma, which is in the path of PTGER4, which encodes a prostaglandin receptor, and poses

linkage disequilibrium Linkage disequilibrium, often abbreviated to LD, is a term in population genetics referring to the association of genes, usually linked genes, in a population. It has become an important tool in medical genetics and other fields In defining LD, it ...

( LD ), which is the association between two alleles located near each other on a chromosome, which assumes more frequent than expected at random co-inheritance, as it presents a great LD with other SNPs associated with the disease of

spondylitis Spondylitis is an inflammation of the vertebrae. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joints, as well, which itself is called spondylarthritis. __TOC__ Types Pott disease is a tuberculous d ...

. In addition, many loci associated with allergies are near genes involved in the differentiation of

T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

. The association, according to the analysis can be eQTL since said SNP associated gene causes BCL6 expression, a transcription factor that suppresses the differentiation of T helper type 2 cells in animal models. Many

autoimmune diseases An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that ...

are associated with increased activation of the Th1 response, while allergies are associated with the activity of TH2, so that these results can help to identify factors that influence the balance between the activity of TH1 and TH2, as well as elements which contribute to both responses.De Jager, P. L., Jia, X., Wang, J., de Bakker, P. I., Ottoboni, L., Aggarwal, N. T., ... & Oksenberg, J. R. (2009). Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature genetics, 41(7), 776-782.

References

{{reflist

External links

''GDS'' (Genomic Data Sharing), in NIH

''Published catalogue of GWAS'', in NIH
Allergology