Genome-wide analysis of runs of homozygosity identifies new susceptibility regions of lung cancer in Han Chinese

Runs of homozygosity (ROHs) are a class of important but poorly studied genomic variations and may be in-volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study (1,473 cases and 1,962 controls) in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi-ate and long ROHs, to evaluate their association with lung cancer risk using existing genome-wide single nucleotide polymorphism (SNP) data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer (odds ratio = 0.63; 95% confidence interval: 0.51-0.77; P = 4.78×10-6 ), while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23.1 that was con-sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.