Heritability and molecular-genetic basis of the P3 event-related brain potential: a genome-wide association study.

Illustration of the common pathway model for deriving genetic and environmental factor scores. P3 amplitude at three sites (P3, Pz, and P4) is due to the influence of a common factor, F, as well as site-specific or unique influences (U1–U3). The factor loadings, λ1 to λ3, are estimates of the magnitude of the influence of F on the three measurements. To identify the model, the variance of F is fixed at 1 and the factor mean is fixed at 0. Under the model, amplitude at a given electrode site, j, equals P3j = αj + λj F + uj, where αj are the intercepts for the amplitude measures (equivalent to the intercept in linear regression) and uj is the unique (residual) influence on each amplitude measure. The common factor, F, is itself influenced (caused) by additional latent factors: A, representing additive genetic influence; C, representing common environmental influence; and E, representing specific environmental influence. Using family data, in which genetic and environmental correlations among family members are known, the magnitude of each latent variable’s influence on F can be estimated, given standard assumptions. Factor variances are fixed at one (not shown), so the total variance in F can be represented as a2 + c2 + e2, using standard tracing rules for path analysis. Because our interest is in the common genetic influence on F, we did not decompose the unique factors into A and C in addition to E.

Q-Q plot for SNP associations with P3 amplitude. The 45° line gives the expected value under the null distribution. The area shaded in gray corresponds to the 95% acceptance region. Median and mean genomic control values are given in the inset in the upper left. N refers to the number of SNPs, which is 10 fewer than the number of SNPs on the array because there was no variation for 10 SNPs in this sample. Q-Q plots in GWAS give the observed p values against the expected p values under the null distribution of no association, although the additive inverse of the common log of p values (−log10[p value]) is used in order to emphasize small p values. Because the vast majority of SNPs are not expected to be associated with a given phenotype, observed p values should conform closely to their expected values, falling on or very close to the 45° line depicted.

Q-Q plot for SNP associations with the genetic factor score. The 45° line gives the expected value under the null distribution of no association. The area shaded in gray corresponds to the 95% acceptance region. Median and mean genomic control values are given in the inset in the upper left. N refers to the number of SNPs that were actually polymorphic in this sample, which is smaller than the P3 sample because subjects without amplitude values for all three parietal electrodes were dropped. Q-Q plots in GWAS give the observed p values against the expected p values under the null distribution, although the additive inverse of the common log of p values (−log10[p value]) is used in order to emphasize small p values. Because the vast majority of SNPs are not expected to be associated with a given phenotype, observed p values should conform closely to their expected values, falling on or very close to the 45° line depicted.

Manhattan plot of individual SNP associations with P3 amplitude. Manhattan plots also depict the distribution of −log10(p values) but are ordered by SNP location on a chromosome, which provides information about the location of any SNPs associated with small p values. The horizontal line at 7.3 indicates the genome-wide significance level (5E-08). The horizontal line at 5 indicates E-05, which is sometimes used to indicate “suggestive” significance.

Manhattan plot of individual SNP associations with the genetic factor score. Manhattan plots also depict the distribution of −log10(p values) but are ordered by SNP location on a chromosome, which provides information about the location of any SNPs associated with small p values. The horizontal line at 7.3 indicates the genome-wide significance level (5E-08). The horizontal line at 5 indicates E-05, which is sometimes used to indicate “suggestive” significance.