title: A Common Polymorphism in SCN2A Predicts General Cognitive Ability through Effects on PFC Physiology.
abstract: Here we provide novel convergent evidence across three independent cohorts of healthy adults (n = 531), demonstrating that a common polymorphism in the gene encoding the α2 subunit of neuronal voltage-gated type II sodium channels (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher "g" independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort (n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral PFC and dorsal ACC, which support higher cognitive functions. Collectively, these findings fill a gap in our understanding of the genetics of general cognitive ability and highlight a specific neural mechanism through which a common polymorphism shapes interindividual variation in "g."
authors.affiliation: Duke University.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Scult
authors.affiliation: The Zucker Hillside Hospital, Glen Oaks, NY.
authors.forename: Joey W
authors.initials: JW
authors.lastname: Trampush
authors.affiliation: Johns Hopkins School of Medicine.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zheng
authors.affiliation: 23andMe, Inc., Mountain View, CA.
authors.forename: Emily Drabant
authors.initials: ED
authors.lastname: Conley
authors.affiliation: The Zucker Hillside Hospital, Glen Oaks, NY.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: The Zucker Hillside Hospital, Glen Oaks, NY.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.affiliation: U.S. National Institutes of Health.
authors.forename: Dwight
authors.initials: D
authors.lastname: Dickinson
authors.affiliation: Johns Hopkins School of Medicine.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.affiliation: Duke University.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012146:Rest; D055815:Young Adult
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human