Genetic association studies in critically ill patients: a systematic review

Area of Science:

• Genetics
• Critical Care Medicine
• Genomic Epidemiology

Background:

• Critical illness is complex, with genetic factors playing a potential role in disease mechanisms.
• Existing genetic research in critical illness lacks systematic summarization.
• This study addresses the need to compile and assess genetic association studies in critically ill patients.

Purpose of the Study:

• To systematically review and compile genetic association studies in critically ill patients.
• To assess the risk of bias in identified genetic association studies.
• To identify significant genetic variants associated with critical illness traits.

Main Methods:

• Systematic literature review of PubMed, EMBASE, and Cochrane Library.
• Bias risk assessment using a novel tool for genetic association studies.
• Compilation of significant single nucleotide polymorphisms (SNPs) and lookup in genome-wide association studies (GWASs).

Main Results:

• Identified 61 studies on genetic variants in intensive care patients, covering 126 genetic loci.
• 97% of studies showed some or high risk of bias; only 3% (two GWASs) had low risk.
• Two significant SNPs (rs4957796 in FER, rs9508032 in FLT1) and one replicated association (rs2569190 in CD14) were identified, with most associations having high bias.

Conclusions:

• A significant deficiency in high-quality genetic research in critical care medicine was identified.
• The review highlights the need for more rigorous, preferably genome-wide, genetic association studies.
• Enhanced understanding of critical illness mechanisms requires improved study quality and design.