Genetic basis of a cognitive complexity metric

• Published in: PloS one 2015-04, Vol.10 (4), p.e0123886-e0123886
• Main Authors: Hansell, Narelle K, Halford, Graeme S, Andrews, Glenda, Shum, David H K, Harris, Sarah E, Davies, Gail, Franic, Sanja, Christoforou, Andrea, Zietsch, Brendan, Painter, Jodie, Medland, Sarah E, Ehli, Erik A, Davies, Gareth E, Steen, Vidar M, Lundervold, Astri J, Reinvang, Ivar, Montgomery, Grant W, Espeseth, Thomas, Hulshoff Pol, Hilleke E, Starr, John M, Martin, Nicholas G, Le Hellard, Stephanie, Boomsma, Dorret I, Deary, Ian J, Wright, Margaret J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Brain research; Cognition; Cognition & reasoning; Cognitive ability; Complexity; Dementia; Epidemiology; Female; Gene expression; Genetic aspects; Genetic Association Studies; Genetic factors; Genetic markers; Genome-Wide Association Study - methods; Genomes; Heritability; Hospitals; Humans; Intelligence; Loci; Male; Medical imaging; Medical research; Medicine; Memory; Mental disorders; Meta-analysis; Meta-Analysis as Topic; Models, Biological; Neuropeptides; Physiological aspects; Polymorphism, Single Nucleotide; Psychiatry; Psychosis; Quantitative genetics; Quantitative Trait, Heritable; Reasoning; Risk factors; Schizophrenia; Short term memory; Twins; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123886

Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the molecular level, we found preliminary support for four single-marker loci (one in the gene DGKB), and at a gene-based level for the NPS gene, having influence on cognition. These results indicate that genetic sources influencing relational processing are a key component of the genetic architecture of broader cognitive abilities. Further, they suggest a genetic cascade, whereby genetic factors influencing capacity limitation in relational processing have a flow-on effect to more complex cognitive traits, including reasoning and working memory, and ultimately, IQ.