Some linkage peaks detected in previous studies have coincided with candidate genes, most obviously with the GABA receptor and alcohol dehydrogenase genes on chromosome 4. Results from multiple association studies from our own laboratory (Macgregor et al., in press) and others (Edenberg, 2007; Edenberg et al., 2004), particularly on the ADH1B and GABRA2 genes, confirm that variation in these regions does affect alcohol consumption and dependence risk. Our largest linkage peaks on chromosome 4 were around 1.0 for Frequency. One may therefore ask why more substantial linkage to these regions was not found in our study. The likely reason is that the proportion of variance in consumption explained by polymorphisms in these genes is small, probably only a few percent, and so the power of even quite large linkage studies to detect these loci will be low. With low power, some studies will find significant or near-significant linkage and others will not. In addition, some of our negative findings may be due to uneven marker distribution leading to gaps in coverage.
