Genome-wide association studies establish that human intelligence is highly heritable and polygenic

Abstract

General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan1,2. Data from twin and family studies are consistent with a high heritability of intelligence3, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549 692 SNPs and detailed phenotypes on cognitive traits. We estimate that 40% of the variation in crystallized-type intelligence and 51% of the variation in fluid-type intelligence between individuals is accounted for by linkage disequilibrium between genotyped common SNP markers and unknown causal variants. These estimates provide lower bounds for the narrow-sense heritability of the traits. We partitioned genetic variation on individual chromosomes and found that, on average, longer chromosomes explain more variation. Finally, using just SNP data we predicted approximately 1% of the variance of crystallized and fluid cognitive phenotypes in an independent sample (P = 0.009 and 0.028, respectively). Our results unequivocally confirm that a substantial proportion of individual differences in human intelligence is due to genetic variation, and are consistent with many genes of small effects underlying the additive genetic influences on intelligence.

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait

“…Despite the high heritability of intelligence, 12,28,37,38 the progress in the identification of loci consistently associated with variation in its normal range has thus far been limited. 15,17,[38][39][40][41][42] Exceptions are the apolipoprotein E (APOE) gene at older ages 43 and formin binding protein 1-like (FNBP1L), the latter having recently been shown to be associated with both childhood and adulthood intelligence. 15,17 The present approach utilizes the idea that the differentially sized effects of individual mutations located within a gene functionally relevant to the phenotype may range from severe disruptions of protein functioning (resulting in a Mendelian disorder) to smaller effects underlying polygenic variation.…”

“…15,17,[38][39][40][41][42] Exceptions are the apolipoprotein E (APOE) gene at older ages 43 and formin binding protein 1-like (FNBP1L), the latter having recently been shown to be associated with both childhood and adulthood intelligence. 15,17 The present approach utilizes the idea that the differentially sized effects of individual mutations located within a gene functionally relevant to the phenotype may range from severe disruptions of protein functioning (resulting in a Mendelian disorder) to smaller effects underlying polygenic variation. Utilizing prior knowledge on genetics of Mendelian disorders may therefore prove a valuable approach to the identification of genetic variability underlying polygenic traits, with the advantage of requiring considerably smaller sample sizes than GWAS to achieve adequate power.…”

“…Despite its being one of the most heritable human traits (with heritability estimates ranging from 0.6 to 0.8 in adolescence and adulthood 12,13 ), no loci consistently associated with normal-range variation in intelligence have thus far been reported. [13][14][15][16] The two largest genome-wide association studies (GWAS) to date failed to find replicable genome-wide association in SNP-based analyses in adults and children, respectively. 15,17 The 43 genes considered in the present study are a subset of the genes identified in a recent study that used homozygosity mapping, exon enrichment, and next-generation sequencing in consanguineous families with autosomal-recessive intellectual disabilities to identify single, presumably disease-causing variants in 50 novel candidate genes.…”

“…[13][14][15][16] The two largest genome-wide association studies (GWAS) to date failed to find replicable genome-wide association in SNP-based analyses in adults and children, respectively. 15,17 The 43 genes considered in the present study are a subset of the genes identified in a recent study that used homozygosity mapping, exon enrichment, and next-generation sequencing in consanguineous families with autosomal-recessive intellectual disabilities to identify single, presumably disease-causing variants in 50 novel candidate genes. 11 The genome-wide data set of the Netherlands Twin Register (NTR), 18 used in the present study, contains SNP data on 43 of these 50 genes (Table 1), including 1227 genotyped SNPs in total (Supplementary Table S1).…”

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

“…In other words, in contrast to the genome-wide reduction of heterozygosity caused by inbreeding, the reduction of heterozygosity due to assortative mating for a trait is limited to loci associated with the trait. However, if many loci affect the trait-which is the conclusion from genome-wide association studies of complex traits and common disorders, including cognitive ability 17,18 -the trait-specific reduction of heterozygosity might be observed genome-wide even if the effects of individual loci are too small to be observed. Another difference between inbreeding and assortative mating is that the effects of inbreeding are expected to be negative, lowering cognitive ability, whereas the effects of assortative mating affect the high, as well as the low end of the ability distribution, thus increasing genetic variance, that is, when high-ability parents mate assortatively, their children are more likely to be homozygous for variants for high ability, just as offspring of low-ability parents are more likely to be homozygous for variants for low ability.…”