Genetic correlates of the development of theta event related oscillations in adolescents and young adults

Chorlian, David B.; Rangaswamy, Madhavi; Manz, Niklas; Meyers, Jacquelyn L.; Kang, Sun J.; Kamarajan, Chella; Pandey, Ashwini K.; Wang, Jen Chyong; Wetherill, Leah; Edenberg, Howard J.; Porjesz, Bernice

doi:10.1016/j.ijpsycho.2016.11.007

Cited by 16 publications

(27 citation statements)

References 126 publications

(198 reference statements)

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“…From these data, we conclude that measures of neural connectivity can be used to further understanding of how polygenic liability to AD may influence brain function, as well as the importance of examining sex and developmental effects in polygenic associations. We note however, that effect sizes were modest, ranging between 0.15 and 0.21 (beta coefficients ranged from 0.02–0.06), consistent with other developmental studies of EEG phenotypes [54,58].…”

Section: Discussionsupporting

confidence: 89%

“…Association of PRS with EEG coherence trajectories were calculated as described in detail in Chorlian et al [54]. Briefly, to test for association between each PRS and EEG coherence phenotype (27 coherence pairs, 7 frequency bands, 3 PRS levels), a local linear (non-parametric) regression model was calculated, including the PRS as the predictor and the inverse hyperbolic tangent of the coherence measure as the dependent variable.…”

Section: Methodsmentioning

confidence: 99%

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Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

et al. 2019

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Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

et al. 2019

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“…Pandey et al, 2012). Recent genetic studies and the current study have demonstrated associations of KCNJ6 with theta EROs (Kang et al, 2012; Chorlian et al, in press). The current study has indicated that variations in the KCNJ6 SNP (rs702859) influence magnitude of theta ERO power at posterior leads during during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward processing.…”

Section: Discussionsupporting

confidence: 53%

“…Kang et al, 2012). Following up this finding, a recent study from our group examined the effects of KCNJ6 SNPs on developmental trajectories of the same theta ERO phenotypes in auditory and visual oddball tasks in adolescent and young adults (12–25) from the COGA prospective study; significant age- and gender-specific effects were found, with some effects of scalp locality and task modality (Chorlian et al, in press). …”

Section: Introductionmentioning

confidence: 99%

“…The overall goal of the present study is to investigate the genotypic effects of a KCNJ6 SNP (rs702859) on theta EROs during reward processing in subjects (17–25 years old) in the COGA Prospective study. This age range was selected as the study by Chorlian et al (in press) indicated that the effects of this SNP on theta EROs were strongest in this age range of the prospective study. The rationale for selecting rs702859 was three-fold: (i) this SNP had a genome-wide significant association with theta ERO in the previous GWAS study; (ii) this SNP was in high LD with the top genome-wide significant genotyped SNPs, and (iii) this was the only exonic genomewide significant SNP in the KCNJ6 gene.…”

Section: Introductionmentioning

confidence: 99%

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A KCNJ6 gene polymorphism modulates theta oscillations during reward processing

Kamarajan

Pandey

Chorlian

et al. 2017

International Journal of Psychophysiology

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Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1,601 adolescent and young adult offspring within the age-range of 17–25 years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5–7.5 Hz, 200–500 ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA > AG > GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible “protective” factors, or as indices of delays in brain maturation (i.e., lack of frontalization).

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Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

et al. 2021

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Genetic correlates of the development of theta event related oscillations in adolescents and young adults

Cited by 16 publications

References 126 publications

Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

A KCNJ6 gene polymorphism modulates theta oscillations during reward processing

Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

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