Mendelian and polygenic inheritance of intelligence: A common set of causal genes? Using next-generation sequencing to examine the effects of 168 intellectual disability genes on normal-range intelligence

Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been robustly associated with normal-range intelligence to date. This is largely ascribed to the high polygenicity of intelligence, i.e., to its being su...

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Veröffentlicht in:Intelligence (Norwood) Jg. 49; S. 10 - 22
Hauptverfasser: Franić, Sanja, Dolan, Conor V., Broxholme, John, Hu, Hao, Zemojtel, Tomasz, Davies, Garreth E., Nelson, Kelly A., Ehli, Erik A., Pool, René, Hottenga, Jouke-Jan, Ropers, H.-Hilger, Boomsma, Dorret I.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Elsevier Inc 01.03.2015
Elsevier Science Ltd
Schlagworte:
Ascription
Biological variation
Candidates
Family research
Family studies
Genes
Genetics
Genomics
Genotype & phenotype
Heritability
Individual differences
Inheritance
Inheritance and succession
Intellectual disabilities
Intelligence
Intelligence tests
Learning disabilities
Mutation
Next-generation sequencing
People with disabilities
Phenotypes
Polygenic prediction
Variants
Genetics
Next-generation sequencing
Intelligence
Polygenic prediction
ISSN:0160-2896, 1873-7935
Online-Zugang:Volltext
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Abstract Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been robustly associated with normal-range intelligence to date. This is largely ascribed to the high polygenicity of intelligence, i.e., to its being subject to the effects of a large number of genes of individually small effect. Intellectual disability, on the other hand, frequently involves large effects of single genetic mutations, many of which have been identified. The present paper aims to 1) introduce the reader to the current state of genetic intelligence research, including next-generation sequencing and the analysis of rare genetic variants, and 2) examine the possible effects of known disability genes on normal-range intelligence. The rationale for the latter rests on the fact that genetic variants affecting continuous, polygenic traits are often concentrated in the same areas of the genome as those underlying related monogenic phenotypes. Using an existing pool of known intellectual disability genes, we constructed a set of 168 candidate genes for normal-range intelligence, and tested their association with intelligence in 191 individuals (aged 5–18) sampled from the high and low ends of the IQ distribution. In particular, we 1) employed exon sequencing to examine the possible effects of rare genetic variants in the 168 genes, and 2) used polygenic prediction to examine the overall effect of common genetic variants in the candidate gene set in a larger sample (N=2125, mean age 20.4, SD=14.1). No significant association between the candidate gene set and intelligence was detected. •To date, no genetic variants have been robustly associated with intelligence.•In contrast, many genes for intellectual disability (ID) have been identified.•We hypothesize that ID genes may be enriched with genetic variants associated with intelligence.•To this end, we test for an association between intelligence and 168 known ID genes.•No association is detected.
AbstractList Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been robustly associated with normal-range intelligence to date. This is largely ascribed to the high polygenicity of intelligence, i.e., to its being subject to the effects of a large number of genes of individually small effect. Intellectual disability, on the other hand, frequently involves large effects of single genetic mutations, many of which have been identified. The present paper aims to 1) introduce the reader to the current state of genetic intelligence research, including next-generation sequencing and the analysis of rare genetic variants, and 2) examine the possible effects of known disability genes on normal-range intelligence. The rationale for the latter rests on the fact that genetic variants affecting continuous, polygenic traits are often concentrated in the same areas of the genome as those underlying related monogenic phenotypes. Using an existing pool of known intellectual disability genes, we constructed a set of 168 candidate genes for normal-range intelligence, and tested their association with intelligence in 191 individuals (aged 5-18) sampled from the high and low ends of the IQ distribution. In particular, we 1) employed exon sequencing to examine the possible effects of rare genetic variants in the 168 genes, and 2) used polygenic prediction to examine the overall effect of common genetic variants in the candidate gene set in a larger sample (N=2125, mean age 20.4, SD=14.1). No significant association between the candidate gene set and intelligence was detected.
Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been robustly associated with normal-range intelligence to date. This is largely ascribed to the high polygenicity of intelligence, i.e., to its being subject to the effects of a large number of genes of individually small effect. Intellectual disability, on the other hand, frequently involves large effects of single genetic mutations, many of which have been identified. The present paper aims to 1) introduce the reader to the current state of genetic intelligence research, including next-generation sequencing and the analysis of rare genetic variants, and 2) examine the possible effects of known disability genes on normal-range intelligence. The rationale for the latter rests on the fact that genetic variants affecting continuous, polygenic traits are often concentrated in the same areas of the genome as those underlying related monogenic phenotypes. Using an existing pool of known intellectual disability genes, we constructed a set of 168 candidate genes for normal-range intelligence, and tested their association with intelligence in 191 individuals (aged 5–18) sampled from the high and low ends of the IQ distribution. In particular, we 1) employed exon sequencing to examine the possible effects of rare genetic variants in the 168 genes, and 2) used polygenic prediction to examine the overall effect of common genetic variants in the candidate gene set in a larger sample (N=2125, mean age 20.4, SD=14.1). No significant association between the candidate gene set and intelligence was detected. •To date, no genetic variants have been robustly associated with intelligence.•In contrast, many genes for intellectual disability (ID) have been identified.•We hypothesize that ID genes may be enriched with genetic variants associated with intelligence.•To this end, we test for an association between intelligence and 168 known ID genes.•No association is detected.
Author Boomsma, Dorret I.
Ehli, Erik A.
Franić, Sanja
Nelson, Kelly A.
Dolan, Conor V.
Hu, Hao
Ropers, H.-Hilger
Zemojtel, Tomasz
Hottenga, Jouke-Jan
Broxholme, John
Davies, Garreth E.
Pool, René
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  givenname: Conor V.
  surname: Dolan
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  organization: VU University Amsterdam, The Netherlands
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  surname: Broxholme
  fullname: Broxholme, John
  organization: Wellcome Trust Centre for Human Genetics, University of Oxford, UK
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  surname: Hu
  fullname: Hu, Hao
  organization: Max Planck Institute for Molecular Genetics, Berlin, Germany
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  surname: Zemojtel
  fullname: Zemojtel, Tomasz
  organization: Max Planck Institute for Molecular Genetics, Berlin, Germany
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  surname: Davies
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  organization: Avera Institute for Human Genetics, Sioux Falls, USA
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  organization: Avera Institute for Human Genetics, Sioux Falls, USA
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  surname: Ehli
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  organization: Avera Institute for Human Genetics, Sioux Falls, USA
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  surname: Pool
  fullname: Pool, René
  organization: VU University Amsterdam, The Netherlands
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  surname: Hottenga
  fullname: Hottenga, Jouke-Jan
  organization: VU University Amsterdam, The Netherlands
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  surname: Ropers
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  organization: Max Planck Institute for Molecular Genetics, Berlin, Germany
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  givenname: Dorret I.
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  organization: VU University Amsterdam, The Netherlands
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Snippet Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been...
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SubjectTerms Ascription
Biological variation
Candidates
Family research
Family studies
Genes
Genetics
Genomics
Genotype & phenotype
Heritability
Individual differences
Inheritance
Inheritance and succession
Intellectual disabilities
Intelligence
Intelligence tests
Learning disabilities
Mutation
Next-generation sequencing
People with disabilities
Phenotypes
Polygenic prediction
Variants
Title Mendelian and polygenic inheritance of intelligence: A common set of causal genes? Using next-generation sequencing to examine the effects of 168 intellectual disability genes on normal-range intelligence
URI https://dx.doi.org/10.1016/j.intell.2014.12.001
https://www.proquest.com/docview/1659816659
https://www.proquest.com/docview/1727679290
Volume 49
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