We had a major discussion before our 2010 paper where I argued that rare variants should have been included. Ten years after there is a nice paper using massive exome sequencing that finally includes them. The respiratory tract isn’t so much influenced by rare variants but there is a strong effect in the immune system.
And there is another interesting fact.
Surveying the contribution of rare variants to the genetic architecture of human disease through exome sequencing of 177,882 UK Biobank participants …if we look at the …. European population who are carriers of a filaggrin (FLG) PTV, we find those carriers have significantly higher risk for well-known associations, such as dermatitis … and asthma … Concomitant increases in vitamin D levels suggest risk of melanoma and basal cell carcinoma in FLG PTV carriers could be attributable to increased sensitivity to ultraviolet B radiation.
So far, I have only assumed some asthma/allergy priming effect of oral vitamin D in the newborn gut.
This paper now argues for an increased vitamin D sensitivity in the skin of FLG dermatitis patients which is interesting given the largely contradictory data of serum vitamin D and atopic dermatitis. Maybe dermatologists should focus their research more on local vitamin D turnover?