Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions

Abstract

Experimental approaches to genetic studies of complex traits evolve with technological advances. How do discoveries using different approaches advance our knowledge of the genetic architecture underlying complex diseases/traits? Do most of the findings of newer techniques, such as genome-wide association study (GWAS), provide more information than older ones, for example, genome-wide linkage study? In this review, we address these issues by developing a nicotine dependence (ND) genetic susceptibility map based on the results obtained by the approaches commonly used in recent years, namely, genome-wide linkage, candidate gene association, GWAS and targeted sequencing. Converging and diverging results from these empirical approaches have elucidated a preliminary genetic architecture of this intractable psychiatric disorder and yielded new hypotheses on ND etiology. The insights we obtained by putting together results from diverse approaches can be applied to other complex diseases/traits. In sum, developing a genetic susceptibility map and keeping it updated are effective ways to keep track of what we know about a disease/trait and what the next steps may be with new approaches.

Figure 1

The ND genetic susceptibility map with nominated linkage peaks and candidate genes, as suggested by genome-wide linkage, hypothesis-driven candidate gene association (CAS), genome-wide association (GWAS), and targeted sequencing (next-generation sequencing; NGS) studies. Linkage peaks are marked in light gray; CAS, GWAS, and NGS results are presented as gene names at the outer, middle, and inner rings, respectively.