No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity

PLoS One. 2015 Sep 17;10(9):e0135983. doi: 10.1371/journal.pone.0135983. eCollection 2015.

Abstract

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Frequency
  • Genomics
  • Genotype
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza, Human / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • RNA, Viral / genetics
  • Risk Factors
  • Severity of Illness Index

Substances

  • RNA, Viral

Grant support

Fundign for this work came from Instituto de Salud Carlos III (Madrid, Spain; www.isciii.es) grant GR09/0032. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.