Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

Autor/inn/en	Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.
Titel	Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes
Quelle	In: Journal of the American Academy of Child & Adolescent Psychiatry, 51 (2012) 4, S.432-440 (9 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0890-8567
DOI	10.1016/j.jaac.2012.01.006
Schlagwörter	Attention Deficit Hyperactivity Disorder; Intelligence; Genetics; Brain; Cognitive Ability; Identification; Correlation; Cognitive Development; Prediction; Individual Differences; Research; Data Analysis + Suchen Sie Ihr Suchwort? Intelligenz; Klugheit; Humangenetik; Gehirn; Denkfähigkeit; Identifikation; Identifizierung; Korrelation; Kognitive Entwicklung; Vorhersage; Individueller Unterschied; Forschung; Auswertung
Abstract	Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally homogeneous family sample of 656 individuals with at least one child affected by attention-deficit/hyperactivity disorder (ADHD). Results: Haplotype trend regression analysis with sliding four-SNP windows identified haplotypes of genome-wide significance in genes involved in synaptic signaling ("KIF16B"; p = 1.27E-08) and neurodevelopment ("PAX5"; p = 3.58E-08), and highlight findings from a recent genetic study of cognitive ability ("RXRA"; p = 7.7E-08; "GYPC"; p = 2.5E-07). Further interrogation of SNPs within top haplotypes reveals that the minor alleles are associated with higher intelligence, whereas others are associated with relatively lower (but still average range) intelligence. Effects of the eight genes are additive, as a greater number of the associated genotypes in a given individual predict higher intelligence (p = 5.36E-08) and account for 8% of variance in intelligence. Conclusions: Analyses that examine additive genetic effects may be useful in identifying regions where the additive effects of SNPs have a significant effect on phenotype. These results describe novel variants and additive effects of genes involved in brain development on variability in intelligence within an ADHD sample. The precise mechanisms of these loci in relation to determining individual differences in general cognitive ability require further investigation. (Contains 3 tables and 3 figures.) (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10