Initially, data were collected from 139 sibling pairs (Wilhelmsen et al., 2003). Variance component analysis found a significant LOD (Log of Odds) score peak of 3.2 for the SHAS score at the 10q terminal region. Of the genes located at 10qter, CYP2E1 has a known involvement with ethanol metabolism. The CYP2E1 enzyme metabolizes ethanol and acetaminophen, as well as many toxicologic and carcinogenic compounds and can be induced by ethanol and nicotine (Tanaka et al., 2000). In the second stage of the study, when 99 newly collected sibling pairs were added (Schuckit et al., 2005), the peak at 10qter was significantly diminished. As will be described in this paper, it was initially assumed that the diminishment was due to locus heterogeneity, but ultimately the reduced evidence for linkage was explained by a single family with extreme and unreliable phenotypes.
