TY - JOUR
T1 - Intelligence
T2 - Shared genetic basis between Mendelian disorders and a polygenic trait
AU - Franić, Sanja
AU - Groen-Blokhuis, Maria M.
AU - Dolan, Conor V.
AU - Kattenberg, Mathijs V.
AU - Pool, René
AU - Xiao, Xiangjun
AU - Scheet, Paul A.
AU - Ehli, Erik A.
AU - Davies, Gareth E.
AU - Van Der Sluis, Sophie
AU - Abdellaoui, Abdel
AU - Hansell, Narelle K.
AU - Martin, Nicholas G.
AU - Hudziak, James J.
AU - Van Beijsterveldt, Catherina E.M.
AU - Swagerman, Suzanne C.
AU - Hulshoff Pol, Hilleke E.
AU - De Geus, Eco J.C.
AU - Bartels, Meike
AU - Ropers, H. Hilger
AU - Hottenga, Jouke Jan
AU - Boomsma, Dorret I.
N1 - Funding Information:
Funding was obtained from the European Science Council (ERC Advanced, 230374), the Netherlands Organization for Scientific Research (NWO: grants 480-04-004, 051.02.060, SPI56-464-14192, NWO/MaGW: VIDI-452-12-014), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI NL, 184.021.007), the VU University’s Institute for Health and Care Research (EMGO+), Neuroscience Campus Amsterdam (NCA), Avera Institute, Sioux Falls, South Dakota (USA), and the National Institutes of Health: Grand Opportunity grant 1RC2MH089951-01. Statistical analyses were partly carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI Posthuma) and the Dutch Brain Foundation and the VU University Amsterdam. This work is part of the programme of BiG Grid, the Dutch e-Science Grid, which is financially supported by the NWO.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/10/22
Y1 - 2015/10/22
N2 - 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.
AB - 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.
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U2 - 10.1038/ejhg.2015.3
DO - 10.1038/ejhg.2015.3
M3 - Article
C2 - 25712083
AN - SCOPUS:84944161035
SN - 1018-4813
VL - 23
SP - 1378
EP - 1383
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 10
ER -