A. What is genome wide association and why might it be useful for studies of the molecular bases of heritable influences on vulnerability to addiction and related phenotypes? One way to view genome wide association is in relationship to linkage based genome scanning, since most of the efforts to “positionally clone” gene variants for complex human disorders (eg those that are likely to be caused by multiple genetic and environmental factors) have used linkage-based methods. Linkage asks how addiction phenotypes and genetic markers (typically genotyped approximately every 1/400th – 1/1,000th of the genome) move together through pedigrees of closely-related individuals. Chromosomal regions that contain marker alleles that move through pedigrees together with the trait are said to be “linked” to the trait. Many loci with nominally-significant linkage to addiction phenotypes have been identified [22–31] (further references in [32]). Several of the loci identified in independent linkage studies do overlap. However, the large numbers of reported linkage-based studies of addictions yield large numbers of nominally-positive results that cover virtually all chromosomes. These widespread results may not converge more than expected by chance, as we have documented in recent analyses of the reported data for linkage to smoking [32].
