title: Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait.
abstract: Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sanja
authors.initials: S
authors.lastname: Franić
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Groen-Blokhuis
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.|Department of Psychological Methods, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Conor V
authors.initials: CV
authors.lastname: Dolan
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mathijs V
authors.initials: MV
authors.lastname: Kattenberg
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Pool
authors.affiliation: Division of OVP, Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Division of OVP, Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Scheet
authors.affiliation: Avera Institute for Human Genetics, Avera McKennan Hospital, University Health Center, Sioux Falls, SD, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: Avera Institute for Human Genetics, Avera McKennan Hospital, University Health Center, Sioux Falls, SD, USA.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
authors.affiliation: Section Functional Genomics, Department of Clinical Genetics, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: van der Sluis
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.affiliation: Genetic Epidemiology, Molecular Epidemiology and Neurogenetics Laboratories, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Narelle K
authors.initials: NK
authors.lastname: Hansell
authors.affiliation: Genetic Epidemiology, Molecular Epidemiology and Neurogenetics Laboratories, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Department of Psychiatry and Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hudziak
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Catherina E M
authors.initials: CE
authors.lastname: van Beijsterveldt
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Swagerman
authors.affiliation: Neuroimaging Research Group, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hilleke E
authors.initials: HE
authors.lastname: Hulshoff Pol
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Meike
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: H Hilger
authors.initials: HH
authors.lastname: Ropers
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing / Q000379:methods; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable