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

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Genes involved in rare cognitive disorders also influence general intelligence. This study found associations between specific genes and intelligence in a large population, highlighting shared genetic underpinnings between rare and common traits.

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Area of Science:

  • Human Genetics
  • Quantitative Trait Genetics
  • Neurogenetics

Background:

  • Genetic basis of human traits often shows overlap between monogenic disorders and quantitative traits.
  • Genes implicated in rare Mendelian disorders can inform the study of complex traits.

Purpose of the Study:

  • To investigate the effect of genes associated with autosomal recessive cognitive disorders on general intelligence.
  • To explore the shared genetic etiology between monogenic cognitive disorders and normal-range intelligence.

Main Methods:

  • Association study in an unselected Dutch population (N=1316).
  • Utilized single-nucleotide polymorphism (SNP)-based and gene-based association testing.
  • Examined the impact of 43 candidate genes.

Main Results:

  • Detected significant associations between intelligence and the studied genes.
  • Identified ELP2, TMEM135, PRMT10, and RGS7 as genes with the strongest associations with intelligence.
  • Demonstrated relevance of genes from monogenic disorders to normal-range intelligence.

Conclusions:

  • Genes implicated in monogenic cognitive disorders contribute to the genetic architecture of normal-range intelligence.
  • Knowledge from monogenic disorders is valuable for uncovering genetic variability in complex traits.
  • Supports a shared genetic basis between rare and common cognitive phenotypes.