Aim: Despite genes on the sex chromosomes contributing to many sexually dimorphic traits, associations on the X-chromosome have been overlooked in previous genome-wide association scans (GWAS) of asthma. Our aim is to impute and test genetic variants on the X-chromosome for association with asthma risk.

Hypotheses: Genetic variants on the X-chromosome contribute to asthma risk and these can be identified through a well powered meta-analysis of results from GWAS of asthma.

Independent variable: Individual genotyped or imputed SNPs located in the X-chromosome, coded as allelic dosage and assuming a dosage compensation model (see below).

Dependent variable: Binary phenotype (ie case-control status) with affected individuals defined as those individuals who reported in any of the available ALSPAC surveys to have been diagnosed by a doctor with asthma. So lifetime self-reported asthmatics. Unaffected individuals are defined as those individuals who never reported to have asthma in any survey.

Confounding variable: None.

Analysis plan: Perform association analysis of SNP dosage after applying standard QC filters (eg. MAFgreater than 1%, HW P-value [in females] greater than 10-6, call rate greater than 95%, imputation info/r2 greater than =0.3) and excluding samples of non-European ancestry. Analyse males and females separately and assume a dosage compensation model (ie. equate hemizygous male to homozygous female, see Clayton 2008), such that the allelic dosage extremes for males are 0 (if A/-, which is the same as for AA females) and 2 (if B/-, which is the same as for BB females)