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In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Within the population-based Finnish twin sample, Finn Twin16, we previously performed multivariate twin analyses to extract latent genetic factors, which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency × quantity, frequency of heavy drinking, frequency of intoxication and maximum drinks in a 24-hour period) and problems (the Rutgers Alcohol Problem Index- RAPI and the Mälmö-modified Michigan Alcohol Screen Test- Mm MAST) in 3065 twins. In the present study, we examined the association between 31 DRD2/ ANKK1 single-nucleotide polymorphisms ( SNPs) and the genetic factor scores generated by twin analyses in a subset of Finn Twin16 ( n = 602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score, which represents shared genetic variance across alcohol measures, and a alcohol problems genetic factor score, which loads onto the two indices of problematic drinking ( MAST and RAPI). After correction for multiple testing across SNPs and phenotypes, of the 31 SNPs genotyped across DRD2/ ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score ( P = 0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing two independent signals after accounting for linkage disequilibrium, showed significant association with the alcohol problems genetic factor score ( P = 0.005, P = 0.005, P = 0.003, P = 0.003). In this study, we provide additional positive evidence for the association between DRD2/ ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggest that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association. [ABSTRACT FROM AUTHOR]

To study sources of individual differences in pubertal development, the authors fit a sex-limitation common factor model to data reported, at ages 11 and 14 years, by 1,891 twin pairs on items that comprise the Pubertal Development Scale (PDS; A. C. Petersen, L. Crockett, M. Richards, & A. Boxer, 1988). The model divides variation into a general pubertal factor and item-specific variation and, in addition, decomposes it into constituent sources. In both boys and girls, genetic influences made the largest contribution to variance common to PDS items. Genetic and nonshared environmental factors accounted for variation specific to PDS items in boys, whereas for girls, common environmental influences were added for growth spurt and menarcheal status. For both common and item-specific variation, genetic effects were partially sex specific. Subsidiary analyses found accelerated maturation in both boys and girls who at age 14 were reared in father-absent homes. [ABSTRACT FROM AUTHOR]

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and traitcomponent analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22q23 locus probably contains one or more migraine susceptibility variants. [ABSTRACT FROM AUTHOR]