Computational protocol: Musical Aptitude Is Associated with AVPR1A-Haplotypes

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Protocol publication

[…] A total of 484 individuals were included in the pedigrees and thus in the genetic analyses. Variance component linkage analysis (SOLAR) was used to calculate the heritability estimates for all phenotypes, namely the test scores of the three musical aptitude tests KMT, SP, and ST, the combined score (denoted with COMB), as well as creativity and its subtypes composing, improvising and arranging. The combined music score (COMB) was computed as the sum of the separate scores of the three individual test results, where KMT music score was first scaled to the same range as the other music scores (ranging from 25 to 50 pts). An exact inverse normal transformation was subsequently performed on all the continuous phenotypes to ensure a normal distribution. Sex and age were routinely included as covariates in all analyses.Genotype incompatibilities were searched with PedCheck . PEDSTATS was used to check the Hardy-Weinberg (HWE) equilibrium. No departure from HWE was observed for any of the markers. Marker allele frequencies were estimated by maximum likelihood in multigenerational families with SOLAR. IBD allele sharing probabilities were computed in a multipoint fashion using the software package Simwalk2.For quantitative traits, family-based genetic association analyses were conducted using the program QTDT version 2.5.1 (http://www.sph.umich.edu/csg/abecasis/QTDT/) . QTDT incorporates variance components methodology in the analysis of family data and includes exact estimation of p-values for analysis of small samples and non-normal data. Linkage and association are considered simultaneously and QTDT also enables taking covariates into consideration when evaluating the genetic association .FBAT/HBAT (family-/haplotype-based association test) version 2.0.2c (http://www.biostat.harvard.edu/˜fbat/default.html) was used to calculate family based association for creativity in music and its endophenotypes as well as all haplotypes; and also to ensure the results for quantitative phenotypes evaluated with QTDT. FBAT tests for association and linkage in pedigrees, using the general test statistic Z , which is based on a linear combination of offspring genotypes and traits. The null hypothesis is “no association and no linkage” between the marker locus and any trait-influencing locus. The alternative hypothesis states there is both association and linkage. FBAT handles pedigrees by breaking each pedigree into all possible nuclear families, and evaluating their contribution to the test statistic independently. A family is informative when it has a non-zero contribution to the FBAT statistic. Covariates can be included via estimation of a regression model in a separate statistical program; here we used SPSS. The covariates were sex and age for music test scores. The residuals of the model can then be used instead of the original traits Yij in the expression of the test statistic. FBAT additionally allows for multiallelic test for multiallelic markers and haplotypes, where the overall association and linkage of the marker/ markers is evaluated, circumventing the locus-wise multiple testing issues, but possibly losing some power. In addition, all results were controlled for multiple testing using permutation on FBAT/HBAT and QTDT. Here, we report both the multiallelic test results as well as single allelic tests. The minimum frequency of alleles and haplotypes to be taken into consideration was set at 0.05. Note, that while all possible two-marker haplotypes of RS1, RS3 and AVR were tested, the three-marker haplotypes RS3-RS1-AVR were not because HBAT cannot handle the high number (91) of different haplotypes with these three markers. In addition to the default, i.e. additive model of gene function, the dominant and recessive were also tested. However, no significant deviations from results by additive tests were observed; thus, these results are not included in the present article. […]

Pipeline specifications

Software tools PedCheck, PEDSTATS, SimWalk2, QTDT, FBAT
Application GWAS
Organisms Homo sapiens
Chemicals Arginine Vasopressin, Serotonin