RT Journal Article SR Electronic T1 Genomic analysis of family data reveals additional genetic effects on intelligence and personality JF bioRxiv FD Cold Spring Harbor Laboratory SP 106203 DO 10.1101/106203 A1 W. David Hill A1 Ruben C. Arslan A1 Charley Xia A1 Michelle Luciano A1 Carmen Amador A1 Pau Navarro A1 Caroline Hayward A1 Reka Nagy A1 David J. Porteous A1 Andrew M. McIntosh A1 Ian J. Deary A1 Chris S. Haley A1 Lars Penke YR 2017 UL http://biorxiv.org/content/early/2017/06/05/106203.abstract AB Pedigree-based analyses of intelligence have reported that genetic differences account for 50-80% of the phenotypic variation. For personality traits these effects are smaller, with 34-48% of the variance being explained by genetic differences. However, molecular genetic studies using unrelated individuals typically report a heritability estimate of around 30% for intelligence and between 0% and 15% for personality variables. Pedigree-based estimates and molecular genetic estimates may differ because current genotyping platforms are poor at tagging causal variants, variants with low minor allele frequency, copy number variants, and structural variants. Using ∼20 000 individuals in the Generation Scotland family cohort genotyped for ∼700 000 single nucleotide polymorphisms (SNPs), we exploit the high levels of linkage disequilibrium (LD) found in members of the same family to quantify the total effect of genetic variants that are not tagged in GWASs of unrelated individuals. In our models, genetic variants in low LD with genotyped SNPs explain over half of the genetic variance in intelligence, education, and neuroticism. By capturing these additional genetic effects our models closely approximate the heritability estimates from twin studies for intelligence and education, but not for neuroticism and extraversion. We then replicated our finding using imputed molecular genetic data from unrelated individuals to show that ∼50% of differences in intelligence, and ∼40% of the differences in education, can be explained by genetic effects when a larger number of rare SNPs are included. From an evolutionary genetic perspective, a substantial contribution of rare genetic variants to individual differences in intelligence and education is consistent with mutation-selection balance.