The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies

On the basis of eight independent quantitative trait loci (QTL) studies of ethanol (alcohol) preference drinking in mice, a meta-analysis was carried out to examine the replicability of QTLs across studies and to enhance the power of QTL detection and parameter estimation. To avoid genetic heterogen eity, we analyzed only studies of mapping populations derived from the C57B L/6 (B6) and DBA/2 (D2) inbred progenitor strains. Because these studies we re carried out in five different laboratories, there were substantial diffe rences in testing procedure, data analysis, and especially in the choice of mapping population (BXD recombinant inbred strains, F-2, backcross, select ed lines, or congenic strains). Despite this, we found several QTLs that we re sufficiently robust as to appear consistently across studies given the s trengths and weaknesses of the mapping populations employed. These were on Chromosomes (Chrs) 2 (proximal to mid), 3 (mid to distal), 4 (distal), and 9 (proximal to mid). The P value for each of these QTLs, combined across al l applicable studies, ranged from 10(-7) to 10(-15), with the additive effe ct of each QTL accounting for 3-5% of the trait variance extrapolated to an F-2 population. Two other QTLs on Chrs 1 (distal) and 11 (mid) were less c onsistent, but still reached overall significance (P < .0001).