Genome-wide Association Study (GWAS) of Rosacea Symptom Severity

[Guide]

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A genome-wide association study (GWAS) of rosacea symptom severity was conducted by Aponte et al [1] that concluded "All associations with rosacea were novel except for the HLA locus. Two of these loci (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in melanocortin 1 receptor) with an association P value just below the significance threshold (P = 1.3 × 10-7) have been previously associated with skin phenotypes and pigmentation, two of these loci are linked to immuno-inflammation phenotypes (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were differentially expressed in a previously published clinical rosacea transcriptomics study that compared lesional to non-lesional samples. The identified loci provide specificity of inflammatory mechanisms in rosacea, and identify potential pathways for therapeutic intervention." 

"In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located." Wikipedia

"With the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005, researchers now have a set of research tools that make it possible to find the genetic contributions to common diseases." [2]

"Genome wide association studies (GWAS) are a relatively new approach to analyzing genetic sequence and have quickly become a fundamental part of modern genetic studies. Their purpose is to determine alleles that correlate to different diseases and traits." [3]

"Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease." [4]

End Notes

[1] Hum Mol Genet. 2018 Aug 1;27(15):2762-2772. doi: 10.1093/hmg/ddy184.
Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes.
Aponte JL, Chiano MN, Yerges-Armstrong LM, Hinds DA, Tian C, Gupta A, Guo C, Fraser DJ, Freudenberg JM, Rajpal DK, Ehm MG, Waterworth DM.

[2] Genome-Wide Association Studies Fact Sheet, NHGRI, NIH

[3] Genome Wide Association Studies (GWAS), Genetics Generation

[4] Nature Reviews Genetics, ISSN 1471-0064 (online)
Benefits and limitations of genome-wide association studies
Vivian Tam, Nikunj Patel, Michelle Turcotte, Yohan Bossé, Guillaume Paré & David Meyre