For many years, linkage analysis was the primary approach for the genetic mapping of both Mendelian and complex traits with familial aggregation.32, 33 This method was largely supplanted by the wide adoption of GWAS in the middle 2000s. In 2008, we published a comprehensive review of more than 20 published genome-wide linkage studies of smoking behaviour and identified 13 regions, located on chromosomes 3–7, 9–11, 17, 20, and 22, suggestively or significantly linked with various ND measurements in at least two independent samples.34 Since then, only one genome-wide linkage study has been reported, by Hardin et al.,35 finding a linked spot in the same region as in their previous analysis (6q26) using the same sample but a different phenotype.36 In addition, Han et al.37 conducted a meta-analysis of 15 genome-wide linkage scans of smoking behaviour and identified two suggestive (5q33.1–5q35.2 and 17q24.3–q25.3) and one significant (20q13.12–q13.32) linkage regions. In fact, the regions on chromosomes 5 and 20 expand two of the regions reported in our 2008 review. The region on chromosome 17 reported by Han et al.37 verified one of
