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Genetic association of impulsivity in young adults: a multivariate study.

Khadka S, Narayanan B, Meda SA, Gelernter J, Han S, Sawyer B, Aslanzadeh F, Stevens MC, Hawkins KA, Anticevic A, Potenza MN, Pearlson GD - Transl Psychiatry (2014)

Bottom Line: Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis.Para-ICA revealed two significantly correlated genotype-phenotype component pairs.We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components.

View Article: PubMed Central - PubMed

Affiliation: Olin Neuropsychiatry Research Center/Institute of Living, Hartford Healthcare, Hartford, CT, USA.

ABSTRACT
Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype-phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors.

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Quantile-Quantile (Q–Q) plot of P-values for (a) IC1 and (b)IC2.
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fig2: Quantile-Quantile (Q–Q) plot of P-values for (a) IC1 and (b)IC2.

Mentions: No significant inflation was noted in the association between loading coefficients and SNP data(see Figure 2 for Q–Q plot). Partial correlation controlling forcalculated intelligent quotient, socio-economic status, age and sex revealed significantcorrelations between two independent impulsivity-related phenotypic components (IC1 and IC2) withtwo genetic components (GC1 and GC2). GC1 contained 618 SNPs from 304 genes and GC2 comprised 643SNPs from 322 genes. The most significant impulsivity-related measures represented in IC1 werereward-sensitivity and Behavioral-Inhibition system scale scores of BIS/BAS scale.30 The most significant impulsivity-related measures represented in IC2were the non-planning subscale score of the BIS-11 (ref. 29) and thearea under the curve score from the EDT.36 IC1 correlatednegatively with GC1 (r=−0.19, P=0.00008) and IC2 correlatedpositively with GC2 (r=0.22, P=0.000002). Scatter plots of bothcomponent pairs are shown in Figure 3. The top 20 most significant genesfrom each of the genetic components GC1 and GC2 are listed in Tables 2and 3, respectively. Post hoc power analysis revealed powerattained from IC1–GC1 and IC2–GC2 correlation pairs were 99.6% and 98.1%,respectively.


Genetic association of impulsivity in young adults: a multivariate study.

Khadka S, Narayanan B, Meda SA, Gelernter J, Han S, Sawyer B, Aslanzadeh F, Stevens MC, Hawkins KA, Anticevic A, Potenza MN, Pearlson GD - Transl Psychiatry (2014)

Quantile-Quantile (Q–Q) plot of P-values for (a) IC1 and (b)IC2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199418&req=5

fig2: Quantile-Quantile (Q–Q) plot of P-values for (a) IC1 and (b)IC2.
Mentions: No significant inflation was noted in the association between loading coefficients and SNP data(see Figure 2 for Q–Q plot). Partial correlation controlling forcalculated intelligent quotient, socio-economic status, age and sex revealed significantcorrelations between two independent impulsivity-related phenotypic components (IC1 and IC2) withtwo genetic components (GC1 and GC2). GC1 contained 618 SNPs from 304 genes and GC2 comprised 643SNPs from 322 genes. The most significant impulsivity-related measures represented in IC1 werereward-sensitivity and Behavioral-Inhibition system scale scores of BIS/BAS scale.30 The most significant impulsivity-related measures represented in IC2were the non-planning subscale score of the BIS-11 (ref. 29) and thearea under the curve score from the EDT.36 IC1 correlatednegatively with GC1 (r=−0.19, P=0.00008) and IC2 correlatedpositively with GC2 (r=0.22, P=0.000002). Scatter plots of bothcomponent pairs are shown in Figure 3. The top 20 most significant genesfrom each of the genetic components GC1 and GC2 are listed in Tables 2and 3, respectively. Post hoc power analysis revealed powerattained from IC1–GC1 and IC2–GC2 correlation pairs were 99.6% and 98.1%,respectively.

Bottom Line: Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis.Para-ICA revealed two significantly correlated genotype-phenotype component pairs.We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components.

View Article: PubMed Central - PubMed

Affiliation: Olin Neuropsychiatry Research Center/Institute of Living, Hartford Healthcare, Hartford, CT, USA.

ABSTRACT
Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype-phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors.

Show MeSH