rs11174072 (Y_RNA-DUX4L52): Influenza Severity

Key takeaways

• Tested in a genome-wide association study (GWAS) of influenza A(H1N1)2009 severity comparing 49 hospitalized and 107 mild confirmed Spanish patients
• No major host genetic risk factor for severe influenza was detected in the study
• Statistical power was sufficient only for large, quasi-Mendelian effects, not the smaller effects typical of complex traits
• Evidence is preliminary with no independent replication in other cohorts

What the research says A GWAS tested 547,296 genome-wide SNPs in 49 hospitalized (severe) and 107 ambulatory (mild) confirmed influenza A(H1N1)2009 patients in Spain, together with 549 general population controls. No SNP reached the conventional genome-wide significance threshold (p = 5 x 10^-8) when comparing severe versus mild cases, and the study's authors concluded that no major host genetic factor could be identified that explained poor influenza A disease course. Statistical power in the design was judged sufficient to detect highly-penetrant, quasi-Mendelian genetic factors, but not the smaller common-variant effects typical of polygenic traits.

Reported associations

• Influenza A(H1N1)2009 severity: rs11174072, located in the Y_RNA - DUX4L52 locus, was included among the 547,296 SNPs tested genome-wide. No variant at this locus was identified as a significant hit; the closest the study came to a genome-wide significant result was a different SNP, rs28454025 (in an intron of GSK233), which the authors considered likely a false positive. The overall conclusion was that no major genetic determinant of severe influenza A course was identified in this sample.

Evidence quality The sole study examining this locus used a small Spanish cohort of 49 severe and 107 mild influenza A(H1N1)2009 cases plus 549 population controls and screened 547,296 SNPs. The authors explicitly acknowledged that sample sizes were sufficient only for detecting large, highly-penetrant effects; modest effect sizes could neither be confirmed nor excluded. No replication cohort was employed, and no external validation of findings was reported. Evidence for this locus is therefore weak and preliminary, and should be interpreted with caution.

Lifestyle considerations No lifestyle considerations on file for this variant.