Having discussed initially informally and then through email follow-up, we have determined that there are at least 7 cohorts within the bounds of the EAGLE consortium containing phenotypic measurements for allergy. This follows closely to the asthma and atopy analysis efforts that are currently already in motion, however forms a discrete analysis effort which will attempt to identify genetic variation associated with allergic reaction as measures objectively through "skin prick" testing.

The initial cohorts recognized with respect to the carriage of skin-prick measurement are:

ALSPAC - UK

B58C_T1DGC - UK

B58C_WTCCC - UK

LISA - Germany

NFBC 66 - Finland

PIAMA - The Netherlands

RAINE - Australia

Please find attached our proposal for an analysis plan. Our suggestion is a primary analysis combining all cohorts with specific IgE in blood and SPT in order to get sufficient numbers and simply include individuals positive to any of the allergens tested for in the respective cohort.

Since IgE in blood is a more sensitive measure than SPT, we would suggest the initial analysis to be specific IgEgreater than =0.35IU/mL and/or SPT greater than =2mm (I have checked with the SPT cohorts that they will all be able to define various weal sizes). This will result in 25%-50% cases in the cohorts.

As a sensitivity analysis we would suggest also asking for IgEgreater than = 3.5 IU/mL and/or SPTgreater than =3mm. This will reduce the numbers of positive samples with app 20-40% with highest effect in the childhood cohorts.

We propose asking the cohorts for analyses of these 2 cut offs now (both separate and combined analyses.Cohorts with only one of blood IgE or SPT (50%) only have to run 2 analyses).

On the basis of this we can then perform meta-analyses on:

*Low cut off combined

*Higher cut off combined

*Blood IgE and SPT separately

*Adult and child cohorts separately

We propose doing this as a first step. Depending on results we can then consider a second round looking at:

*Multiple sensitizations

*Very high levels of IgE

*High level combined specific IgE/weal against the most common inhalant allergens

We are aware of other, competitive, efforts in this field. Principally, the GABRIEL consortium is currently preparing a large body of work on asthma explicitly, though not allergy. As such, we will attempt to contact this body by way of follow-up, however will restrict primary analyses to those cohorts within the EAGLE consortium.