JCVI: Single Nucleotide Polymorphisms in the REG-CTNNA2 Region of chromosome 2 and NEIL3 Associated With Impulsivity in a Native American Sample.
 
 
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Ehlers CL, Gizer IR, Bizon C, Slutske W, Peng Q, Schork NJ, Wilhelmsen KC

Single Nucleotide Polymorphisms in the REG-CTNNA2 Region of chromosome 2 and NEIL3 Associated With Impulsivity in a Native American Sample.

Genes, Brain, and Behavior. 2016 May 11;

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Abstract

Impulsivity is a multi-faceted construct that, while characterized by a set of correlated dimensions, is centered around a core definition that involves acting suddenly in an unplanned manner without consideration for the consequences of such behavior. Several psychiatric disorders include impulsivity as a criterion, and thus it has been suggested that it may link a number of different behavioral disorders, including substance abuse. Native Americans experience some of the highest rates of substance abuse of all US ethnic groups. The described analyses used data from a low coverage whole genome sequence scan to conduct a genome-wide association study of an impulsivity phenotype in an American Indian community sample (n = 658). Demographic and clinical information were obtained using a semi-structured interview. Impulsivity was assessed using a scale derived from the Maudsley personality inventory that combines both novelty-seeking and lack of planning items. The impulsivity score was tested for association with each variant adjusted for demographic variables, and corrected for ancestry and kinship, using EMMAX. Simulations were conducted to calculate empirical p-values. Genome-wide significant findings were observed for a variant 50 kb upstream from catenin cadherin-associated protein, alpha 2 (CTNNA2), a neuronal specific catenin, in the REG gene cluster. A meta-analysis of genome-wide association studies had previously identified common variants in CTNNA2 as being associated with excitement seeking. A second locus upstream of NEIL3 on chromosome 4 also achieved genome-wide significance. The association between sequence variants in these regions suggests their potential roles in the genetic regulation of this phenotype in this population.