Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor

Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking is well established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18–35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P = 0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who never smoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, no significant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics. © 2016 Indian Academy of Science

ABCA1 polymorphism, a genetic risk factor of harm avoidance

Even though cholesterol homeostasis and self-harm behaviors have shown to be associated, gene polymorphisms of the cholesterol system have not been studied yet in the context of self-harm related personality traits. Here we present an association study between six ABCA1 polymorphisms and temperament scales measured by Cloninger's Temperament and Character Inventory on 253 young adults. An association between ABCA1 rs4149264 and harm avoidance has been observed. This association remained significant after Bonferroni correction. Haplotype analysis confirmed an independent association between rs4149264 and harm avoidance. ABCA1, a cholesterol homeostasis gene, is a candidate gene for harm related personality traits. © 2017 Hogrefe Publishing

Association of GDNF and CNTNAP2 gene variants with gambling

Some form of gambling can be observed in nearly every society, as the gratification felt upon winning in uncertain conditions is universal. A culturally distinct form of gambling, associated with a traditional sporting event of archery known as "teer," is innate to the province of Meghalaya, India. The objective of this study was to find genetic variants underlying this unique form of behavioral addiction. To better understand game-based gambling, we studied genetic variants related to dopaminergic pathways and other genes previously linked to various psychological disorders.This study was carried out on a sample of 196 Indo-Aryan adults from Shillong, Meghalaya. Genotyping of glial cell line-derived neurotrophic factor (GDNF) polymorphisms was carried out using real-time PCR. We further investigated 32 single nucleotide polymorphisms located in the 3' UTR of additional genes of interest using an OpenArray® real-time PCR platform.Case-control analysis revealed a significant association between GDNF variant rs2973033 (p = .00864, χ2 = 13.132, df = 2) and contactin-associated protein-like 2 (CNTNAP2) variant rs2530311 (p = .0448, χ2 = 13.132, df = 2) with gambling.Association of the GDNF gene with gambling could be attributed to its involvement in the development and survival of dopaminergic neurons. Our result is in good agreement with previous data indicating the role of GDNF in certain substance addictions. Several rare variants in the CNTNAP2 gene were also implicated in alcohol addiction in a previous study. This pilot study provides further support for the role of GDNF and CNTNAP2 in addiction behaviors

A végrehajtó funkciók összefüggése a testtömegindexszel és a DRD4-VNTR 7-es alléllal

Absztrakt: Bevezetés és célkitűzés: Szakirodalmi eredmények alapján a kórosan sovány és az elhízott személyek gyengébben teljesítenek végrehajtó funkciókat mérő feladatokban, mint a normál súlyúak. Ismert továbbá, hogy a jutalmazó rendszerben kulcsfontosságú dopaminerg rendszer működésének fontos szerepe lehet a testsúlyszabályozásban és a táplálékfelvételben. A jelen vizsgálat célja az volt, hogy az egészséges spektrumon belül megvizsgáljuk a testtömegindex, egy kandidáns dopaminerg génvariáns és a végrehajtó funkciókat mérő Stroop-feladatban elért teljesítmény összefüggéseit, és mindezek alapján pszichogenetikai következtetéseket vonjunk le. Módszer: Kutatásunkban 152, cukorbetegségben vagy pszichiátriai zavarban nem szenvedő személy vett részt. DNS-izolálás céljából nem invazív mintavételt alkalmaztunk, a résztvevőktől demográfiai, testsúly- és testmagasságadatokat gyűjtöttünk, valamint megoldottak egy számítógépes Stroop-feladatot. 11 fő az alultáplált (átlag-testtömegindex: 17,9 kg/m2), 98 fő a normál súlyú (átlag-testtömegindex: 21,8 kg/m2), 43 fő a túlsúlyos (átlag-testtömegindex: 28,9 kg/m2) testtömegindex-kategóriába került. A testtömegindex és a genotípusok alapján csoportosított személyek átlagos teljesítményét összehasonlítva kerestünk pszichogenetikai összefüggéseket. Eredmények: A testtömegindex és a Stroop-feladat próbáinak típusa szignifikáns interakciót mutatott a hibaszámra (p = 0,045): az inkongruens próbákban a normál-testtömegindexet mutató személyek szignifikánsan kevesebbet hibáztak, mint az alultápláltak vagy a túlsúlyosak. A 7-es allélt hordozók tendenciaszinten többet hibáztak, mint a 7-es allélt nem hordozók. Míg a normál-BMI-kategóriába tartozó személyek genotípusuktól függetlenül hasonlóan alacsony szinten hibáztak, a szélsőséges súlycsoportokba tartozó személyek közül a 7-es alléllal rendelkezők többet hibáztak, mint azok, akik nem hordozták ezt a variánst. Következtetés: A válaszgátlást igénylő feladatok nehezebbek azok számára, akik az átlagostól eltérő testtömegindexet mutatnak. Ez összefüggésben lehet azzal, ahogyan a táplálkozással kapcsolatos jelzőingerekre reagálnak. Orv Hetil. 2019; 160(39): 1554–1562. | Abstract: Introduction and aim: Earlier results in the literature suggest that overweight subjects show weaker performance in executive function tasks as compared to normal weight people. Dopaminergic system is strongly linked to executive functions, body mass regulation and ingestion. The aim of the present study was to examine the possible relationship between DRD4 VNTR 7-repeat allele, body mass index and Stroop performance in a healthy adult population, and to draw psychogenetic conclusions. Method: 152 subjects without diabetic or psychiatric history participated in the study. Along with non-invasive DNA sampling, demographic, weight and height data were collected. The participants also solved the computerized Stroop task. 11 subjects belonged to the underweight (mean body mass index = 17.9 kg/m2), 98 subjects to the normal (mean body mass index = 21.8 kg/m2), and 43 subjects to the overweight (mean body mass index = 28.9 kg/m2) category. After grouping participants according to their body mass index and DRD4 VNTR genotype, we compared their mean performance to investigate the possible psychogenetic associations. Results: Body mass index and stimuli type showed significant interaction on error number (p = 0.045): subjects with normal body mass index made significantly less error as compared to under- and overweight subjects in incongruent trials. The 7-repeat allele carriers made tendentiously more errors than non-carriers. Normal weight people made less error – independently from their genotype –, while subjects with either low or high BMI carrying the 7-repeat allele made more errors compared to non-carriers. Conclusion: Under- and overweight subjects perform weaker where inhibition is necessary in the task. This may reflect their reactions to food-related situations. Orv Hetil. 2019; 160(39): 1554–1562

Association between anxiety and non-coding genetic variants of the galanin neuropeptide

Galanin, an inhibitory neuropeptide and cotransmitter has long been known to co-localize with noradrenaline and serotonin in the central nervous system. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. Pharmacological modulation of galanin signaling and transgenic strategies provide further proof for the involvement of the galanin system in the pathophysiology of mood disorders. Little is known, however, on the dynamic regulation of galanin expression at the transcriptional level. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression.Six single nucleotide polymorphisms (SNP) occurring either in the regulatory 5' or 3' flanking regions or within intronic sequences of the galanin gene have been genotyped with a high-throughput TaqMan OpenArray qPCR system in 526 healthy students (40% males). Depression and anxiety scores were obtained by filling in the Hospital Anxiety and Depression Scale (HADS) questionnaire. Data were analyzed by ANCOVA and Bonferroni correction was applied for multiple testing. Linkage disequilibrium (LD) analysis was used to map two haploblocks in the analyzed region.A single-locus and a haplotype genetic association proved to be statistically significant. In single-marker analysis, the T allele of the rs1042577 SNP within the 3' untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407). Haplotype analysis revealed an association of the rs948854 C_rs4432027_C allele combination with anxiety [F(1,1046) = 4.140, p = 0.042141, η2 = 0.004, power = 0.529]. Neither of these associations turned out to be gender-specific. These promoter polymorphisms are supposed to participate in epigenetic regulation of galanin expression by creating potentially methylatable CpG dinucleotides. The functional importance of the rs1042577_T allele remains to be elucidated

Neurokognitiv endofenotipusok a pszichiatriai genetikaban.

Psychiatric genetics aims to map genetic factors of psychiatric disorders with complex inheritance. The most commonly used phenotype is the categorical variable of the presence or absence of a disease (case-control model). However, the biological background of various psychiatric disease categories often overlaps. Thus, the use of endophenotypes based on specific biological mechanisms seems to be a more efficient approach in genetic association studies. Results confirm that categorical variables as phenotypes are statistically not so sensitive in identification of a genetic association as well-chosen endophenotypes. Current literature advocates a growing significance of analyzing dimensional neurocognitive endophenotypes in genetic association studies, as well as in developing diagnostic category systems with biological backgrounds