Figure 3

Haplotype-guided hierarchical fine mapping. Case–reference comparison of discordant and concordant sibling pairs from the European Cystic Fibrosis Twin and Sibling Study at 17 markers identified a 2.5-kb fragment in the intergenic region on 19q13 between carcinoembryonic antigen-related cell adhesion molecule (CEACAM)3 and the open reading frame LOC388544 (highlighted with dotted lines). After re-sequencing of carriers of contrasting haplotypes for this small genomic fragment, five single-nucleotide polymorphisms were identified that are responsible for the observed association. While this approach was not inspired by a candidate gene hypothesis but only by the markers’ positions, the involvement of genes from the CEACAM family in host defence and innate immunity [63] designates these proteins as likely modifiers of cystic fibrosis, which is known for its cytokine imbalance and pro-inflammatory phenotype. Data from [64].