Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes.

During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999.

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

DNA markers associated with high versus low IQ: the IQ Quantitative Trait Loci (QTL) Project.

General cognitive ability (intelligence, often indexed by IQ scores) is one of the most highly heritable behavioral dimensions. In an attempt to identify some of the many genes (quantitative trait loci; QTL) responsible for the substantial heritability of this quantitative trait, the IQ QTL Project uses an allelic association strategy. Allelic frequencies are compared for the high and low extremes of the IQ dimension using DNA markers in or near genes that are likely to be relevant to neural functioning. Permanent cell lines have been established for low-IQ (mean IQ = 82; N = 18), middle-IQ (mean IQ = 105; N = 21), and high-IQ (mean IQ = 130; N = 24) groups and for a replication sample consisting of even more extreme low-IQ (mean IQ = 59; N = 17) and high-IQ (mean IQ = 142; N = 27) groups. Subjects are Caucasian children tested from 6 to 12 years of age. This first report of the IQ QTL Project presents allelic association results for 46 two-allele markers and for 26 comparisons for 14 multiple-allele markers. Two markers yielded significant (p < .01) allelic frequency differences between the high- and the low-IQ groups in the combined sample-a new HLA marker for a gene unique to the human species and a new brain-expressed triplet repeat marker (CTGB33). The prospects for harnessing the power of molecular genetic techniques to identify QTL for quantitative dimensions of human behavior are discussed.