Genome-Wide Linkage Analysis of the Risk of Contracting a Bloodstream Infection in 47 Pedigrees Followed for 23 Years Assembled From a Population-Based Cohort (the HUNT Study)*

Objectives: Bloodstream infection is an important cause of death worldwide. The main objective of this study was to identify genetic loci linked to risk of contracting a bloodstream infection. Design: Genome-wide linkage analysis. Setting: Population-based, Norwegian cohort, followed between 1995 and 2017. Subjects: Among 69,423 genotyped subjects, there were 47 families with two or more second-degree relatives with bloodstream infection in the follow-up period. There were 365 subjects in these families, of which 110 were affected. Interventions: None. Measurements and Main Results: The cohort was genotyped using Illumina HumanCoreExome (Illumina, San Diego, CA) arrays. Before linkage analysis, single-nucleotide polymorphisms were pruned and clumped. In nonparametric linkage analysis using an exponential model, we found three loci with a suggestive linkage to bloodstream infection, all on chromosome 4, at 46.6 centimorgan (logarithm of odds, 2.3), 57.7 centimorgan (logarithm of odds, 3.2), and 70.0 centimorgan (logarithm of odds, 2.1). At the peak of the lead region are three genes: TLR10, TLR1, and TLR6. Conclusions: Variations in the TLR10/1/6 locus appear to be linked with the risk of contracting a bloodstream infection.