More clues for those reading up on Allergic triggers and genetics, etc.
Batch, you'll be all over this...
Implications for CH???
EDIT: The 'complimentary' Full Article is provided from the ABC news site, so maybe go there first and use their link to Nature Genetics (in blue) to gain access to the full PDF.
I have VPN and can see it, not sure who can or cannot, but I can't download the PDF either...
Source (credited, not plagiarised):
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Full PDF:
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ABC news media:
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Abstract:
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biologyManuel A Ferreira, Judith M Vonk, Hansjörg Baurecht, Ingo Marenholz, Chao Tian, Joshua D Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Jenny van Dongen, Yi Lu, Franz Rüschendorf, Jorge Esparza-Gordillo, Chris W Medway, Edward Mountjoy, Kimberley Burrows, Oliver Hummel, Sarah Grosche, Ben M Brumpton, John S Witte, Jouke-Jan Hottenga, Gonneke Willemsen, Jie Zheng, Elke Rodríguez, Melanie Hotze et al.Nature Genetics (2017) doi:10.1038/ng.3985
Received 13 June 2017 Accepted 06 October 2017
Published online 30 October 2017Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2, 3, 4. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10−8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.Article from ABC news:
Scientists identify genetic risk factors for asthma, hay fever and eczemaMore than 100 genetic risk factors for asthma, hay fever and eczema have been identified in a new study that helps shed light on why these conditions often occur together.
The Australian-led study, published today in Nature Genetics, is the first of its kind to pinpoint genetic risk factors common to all three allergic conditions.
It has long been known that there are links between asthma, hay fever and eczema — someone who has one condition is likely to have others.
"We knew that the three diseases shared many genetic risk factors," said lead author Dr Manuel Ferreira of the QIMR Berghofer Medical Research Institute.
"What we didn't know was exactly where in the genome those shared genetic risk factors were located."
To find out, researchers analysed the genomes of more than 360,000 people and identified 136 positions in the genome that are risk factors for developing the three conditions.
"If you are unlucky and inherit these genetic risk factors from your parents, it will predispose you to all three allergic conditions," Dr Ferreira said.
"It doesn't mean you'll get all three, but you are at a higher risk of all three."
Genes affect immune system cellsThe 136 genetic risk factors identified were found to influence whether 132 nearby genes were switched on or off.
"We think that these genes influence the risk of asthma, hay fever and eczema by affecting how the cells of the immune system work," Dr Ferreira said.
Immunologist professor Mimi Tang from the Murdoch Children's Research Institute said the research offered new insight into how gene variants can increase the risk of the dysregulated immune responses found in allergic diseases.
"There's always been a very strong association between these three conditions," she said.
"What this research has done has helped us to understand that the pathways driving these conditions might be similar."
Environment factors play a roleThe study also looked at how environmental factors affect whether these genes are switched on or off.
"We found that this could be happening for many of the genes we identified," Dr Ferreira said.
"For example, we found one gene — called PITPNM2 — that is more likely to be switched off in people who smoke.
"If this gene is switched off, then the risk of developing allergies increases."
Professor Tang said this finding fits in with the current understanding of what causes allergic disease.
"It's a combination of one's genes and the environments that we're exposed to that determine expression of those genes," she said.
New clues for allergy treatment
By identifying genetic risk factors, researchers will be better able to understand which genes, when not working properly, cause allergic conditions, Dr Ferreira said.
"This knowledge helps us understand why allergies develop in the first place and, potentially, gives us new clues on how they could be prevented or treated," he said.
He said researchers had identified several drugs they believed could target some of the affected genes to treat allergies.
"The first step would be to test those drugs in the laboratory," Dr Ferreira said.
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