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Characteristics of SAPALDIA follow-up participants belonging to the discoveryN1392and replication armN4245and of participants of the Copenhagen City Heart StudyN8273
AffiliationDivision of Genetic EpidemiologyDepartment of Medical GeneticsMolecular and Clinical PharmacologyInnsbruck Medical UniversityInnsbruckAustria.
The strength of this study is that it combines the report of a GWAS on AAT serum levels with meta-analyses of the associations of some of the GWAS top variants with lung functionThe effects of the underlying functional variants are thoroughly investigated resulting in the hitherto largest meta-analysis of PI S and Z on FEV1 in ever-smokersAscertainment and study design of the many participating studies were sufficiently diverse to informatively address heterogeneity in association of common and rarer variants in the SERPINA gene cluster with lung functionThe strength of the discovery sample is the population-based study design and the detailed characterization of the participantsSexage and smoking are important modifiers of AAT blood levels in tetracycline 500mg. the general population43and were included in all regression modelsMore refined smoking variables covering smoking intensity were not included as this information is less complete than smoking status in SAPALDIA and would lower the sample sizeBy excluding samples with elevated hs-CRP values we avoided the masking of AAT deficiencies due to a chronic or acute inflammationOn the methodological sideconditional analysis is a well-established tool for identifying independent signals within a certain locus384950Furthermore1000G imputation was able to point to the causal variant demonstrating its reliability to correctly assign alleles close to the 1MAF threshold.
Presented arelog(10p-values and LDr 2with top-ranking SNP rs2736887purple diamondfor all SNPs in this regionThe blue line shows recombination rate.
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our study has found that patients with high levels of serpina1 have better clinical outcome than those with low levels of serpina1.