hole genome association scan for genetic polymorphisms influencing nformation processing speed

Processing speed is an important cognitive function that is compromised in psychiatric illness (e.g., schizophrenia, depression) and old age; it shares genetic background with complex cognition (e.g., working memory, reasoning). To find genes influencing speed we performed a genome-wide association scan in up to three cohorts: Brisbane (mean age 16 years; N = 1659); LBC1936 (mean age 70 years, N = 992); LBC1921 (mean age 82 years, N = 307), and; HBCS (mean age 64 years, N = 1080). Meta-analysis of the eywords: nformation processing speed ognitive ability enes iological pathways common measures highlighted various suggestively significant (p < 1.21 × 10−5) SNPs and plausible candidate genes (e.g., TRIB3). A biological pathways analysis of the speed factor identified two common pathways from the KEGG database (cell junction, focal adhesion) in two cohorts, while a pathway analysis linked to the GO database revealed common pathways across pairs of speed measures (e.g., receptor ic pro s for binding, cellular metabol research, including result Information processing speed is considered a lower level cogitive process, although it shares a large portion of its genetic ariance with higher order abilities (e.g., reasoning, working memry) (Luciano et al., 2003; Neubauer, 1997). It is a cognitive domain hat is particularly prone to deterioration with ageing (Salthouse, Please cite this article in press as: Luciano, M., et al., Whole genome as processing speed. Biol. Psychol. (2011), doi:10.1016/j.biopsycho.2010.11.0 996); for example, simple reaction time (RT) slows at around 0 years of age and choice RT slows throughout the adult range Der and Deary, 2006). However, similar to complex cognition with hich it is correlated, the genes influencing speed are expected to ∗ Corresponding author at: Psychology, University of Edinburgh, 7 George Square, dinburgh EH8 9JZ, UK. Tel.: +44 131 6 51 5040; fax: +44 131 650 8405. E-mail address: michelle.luciano@ed.ac.uk (M. Luciano). 1 These authors contributed equally to this work. 301-0511/$ – see front matter © 2010 Elsevier B.V. All rights reserved. oi:10.1016/j.biopsycho.2010.11.008 cess). These highlighted genes and pathways will be able to inform future psychiatric disease. © 2010 Elsevier B.V. All rights reserved. be stable across the lifespan (Lyons et al., 2009). Speed is affected (slowed) in psychiatric conditions such as schizophrenia, depression and substance use disorder (Andersson et al., 2010; Jahshan et al., 2009) and RT has even been shown to account for the relationship between IQ and mortality in a cohort followed up until age 70 (Deary and Der, 2005; Latvala et al., 2009). It is therefore an important trait to understand, and in this study, we aim to locate genes influencing chronometric and psychometric processing speed measures via genome wide association. These genes may underlie complex cognition or reflect genetic influences specific to speed because a large portion of genetic variance in processing sociation scan for genetic polymorphisms influencing information 08 speed is independent of higher order ability. Processing speed as measured by elementary cognitive tasks has been used to understand the genetic structure of human mental ability (Baker et al., 1991; Ho et al., 1988; Rijsdijk et al., 1998;