Genome-wide association identifies candidate genes that influence the human electroencephalogram

Abstract

Complex psychiatric disorders are resistant to whole-genome analysis due to genetic and etiological heterogeneity. Variation in resting electroencephalogram (EEG) is associated with common, complex psychiatric diseases including alcoholism, schizophrenia, and anxiety disorders, although not diagnostic for any of them. EEG traits for an individual are stable, variable between individuals, and moderately to highly heritable. Such intermediate phenotypes appear to be closer to underlying molecular processes than are clinical symptoms, and represent an alternative approach for the identification of genetic variation that underlies complex psychiatric disorders. We performed a whole-genome association study on alpha (α), beta (β), and theta (θ) EEG power in a Native American cohort of 322 individuals to take advantage of the genetic and environmental homogeneity of this population isolate. We identified three genes (SGIP1, ST6GALNAC3, and UGDH) with nominal association to variability of θ or α power. SGIP1 was estimated to account for 8.8% of variance in θ power, and this association was replicated in US Caucasians, where it accounted for 3.5% of the variance. Bayesian analysis of prior probability of association based upon earlier linkage to chromosome 1 and enrichment for vesicle-related transport proteins indicates that the association of SGIP1 with θ power is genuine. We also found association of SGIP1 with alcoholism, an effect that may be mediated via the same brain mechanisms accessed by θ EEG, and which also provides validation of the use of EEG as an endophenotype for alcoholism.alcoholism | electroencephalogram | endophenotype | genetics | whole-genome association G enetic studies of behavior and psychiatric disorders are hampered by etiologic heterogeneity of these complex phenotypes. Addiction vulnerability arises from both internalizing (emotional) and externalizing (dyscontrol) behavioral dimensions (1), and both of these broad aspects of behavior are strongly influenced by early life trauma and other gene/environment interactions (2). Etiologic heterogeneity dilutes power to detect genetic effects, and is a reason for failures to detect and replicate genome-wide associations (GWAS) in complex disorders. Increasing sample size does not remove underlying heterogeneity and can introduce additional confounds. In neuropsychiatry, these considerations have led to the use of intermediate phenotypes (or endophenotypes) that are heritable, relevant to disease, and have good measurement properties and assay variation more closely related to gene function (3) as surrogates to probe the underlying biology of complex disorders.

Genetics of impulsive behaviour

“…The effects of variants may be context-dependent, leading to failures to detect loci in the absence of exposure, or in the presence of exposures that overwhelm the effects of genes [125]. The use of intermediate phenotypes that are less subject to environmental perturbation and closer to the function of molecular networks appears to amplify power of GWA [126]. If, despite the lack of evidence from transmission studies, 'epistasis is the rule', it may be necessary to test combinations of common alleles [127].…”

Genetic Research on Sleep, Sleep Disturbances and Associated Difficulties

“…Однако стоит отме-тить, что ассоциация была продемонстрирована только для двух из трех проанализированных выборок. В полногеномном исследовании (Hodgkinson et al, 2010) на выборке 322 американских индейцев найдена связь однонуклеотидных полиморфизмов в гене SGIP1 (SH3-domain GRB2-like endophilin-interacting protein 1) с мощностью тета-диапазона ЭЭГ.…”

Is it possible to extract a fingerprint for early breast cancer via EEG analysis?

“…Other studies have determined that the human electroencephalogram is influenced by the genome and also by a significant number of gene types (SGIP1, ST6GAL-NAC3, and UGDH) [22]. Moreover, it has been shown that specific hereditary genes such as BRCA1 and BRCA2 and proteins such as 14-3-3 [24] affect neuronal reactivity [22,25]. Genetic studies have demonstrated that the aforementioned genes and proteins are associated directly with two types of breast cancer [26][27][28][29]: hereditary and non-hereditary.…”

“…In recent studies some brain activities recorded via EEG have been shown to be associated with particular genes and proteins [22] that play a crucial role in the normal (or, conversely, the abnormal) development of breast cells [23]. Other studies have determined that the human electroencephalogram is influenced by the genome and also by a significant number of gene types (SGIP1, ST6GAL-NAC3, and UGDH) [22]. Moreover, it has been shown that specific hereditary genes such as BRCA1 and BRCA2 and proteins such as 14-3-3 [24] affect neuronal reactivity [22,25].…”

“…The partial decoding of EEG findings has shown that it can be used for diagnostic and prognostic purposes [17][18][19][20][21]. In recent studies some brain activities recorded via EEG have been shown to be associated with particular genes and proteins [22] that play a crucial role in the normal (or, conversely, the abnormal) development of breast cells [23]. Other studies have determined that the human electroencephalogram is influenced by the genome and also by a significant number of gene types (SGIP1, ST6GAL-NAC3, and UGDH) [22].…”