A pioneering study indicate role of GABRQ rs3810651 in ASD severity of Indo-Caucasoid female probands.
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ABSTRACT:
SUBMITTER: Saha S
PROVIDER: S-EPMC7997895 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The severity of autism spectrum disorder (ASD) shows wide variations, though the reason remains unclear. Vitamin D (VitD) deficiency is considered a risk factor for ASD and its supplementation was reported to reduce symptom severity. Since VitD, either synthesized in the skin or absorbed from the food, is transported to the liver by the vitamin D binding protein (DBP), we have analyzed DBP genetic polymorphisms [rs7041 (A/C), rs4588 (G/T), and rs3755967 (C/T)] affecting DBP function [Case = 411; Control = 397], levels of plasma 25(OH)D and DBP [Case = 25; Control = 26], and DBP mRNA expression [Case = 74; Control = 44] in a group of Indo-Caucasoid ASD probands and neurotypical subjects. ASD probands with rs7041'CC', rs4588 'TT', and rs3755967 'TT' genotypes exhibited higher scores for a few traits. Scores for Imitation and Listening response were also higher in the presence of the "A-T" haplotype (rs7041-rs4588). Plasma 25(OH)D and DBP levels as well as DBP mRNA expressions were significantly lower in the ASD probands as compared to the neurotypical subjects. We infer that DBP deficiency, in the presence of risk genetic variants, could be one of the reasons for the reported 25(OH)D deficiency of the ASD probands.
| S-EPMC11336207 | biostudies-literature
Project description:BackgroundAttention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline. Monoamine oxidase A (MAOA) and B (MAOB), mitochondrial outer membrane bound two isoenzymes, mediate degradation of these neurotransmitters and thus regulating their circulating levels. Case-control analyses in different populations, including Indians, suggested involvement of MAOA and MAOB genes in the etiology of ADHD. Due to high heritability rate of ADHD, we tested familial transmission of MAOA and MAOB variants to ADHD probands in 190 nuclear families having ADHD probands from Indo-Caucasoid ethnicity.MethodsSubjects were recruited following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioral traits in probands. Genotyping was performed through PCR-based amplification of target sites followed by DNA-sequencing and/or gel-electrophoresis. Data obtained were analyzed by family based statistical methods.ResultsOut of 58 variants present in the analyzed sites only 15 were found to be polymorphic (30 bp-uVNTR, rs5906883, rs1465107, rs1465108, rs5905809, rs5906957, rs6323, rs1137070 from MAOA and rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324, rs3027440 from MAOB). Statistically significant maternal transmission of alleles to male probands was observed for MAOA rs5905809 'G' (p = 0.04), rs5906957 'A' (p = 0.04), rs6323 'G' (p = 0.0001) and MAOB rs56220155 'A' (p = 0.002), rs2283728 'C' (p = 0.0008), rs2283727 'C' (p = 0.0008), rs3027441 'T' (p = 0.003), rs6324 'C' (p = 0.003), rs3027440 'T' (p = 0.0002). Significantly preferential maternal transmissions of different haplotype combinations to male probands were also noticed (p < 0.05), while female probands did not reveal such transmission bias. Behavioral traits of male probands exhibited significant association with gene variants. Age of the mother at pregnancy also revealed association with risk variants of male probands.ConclusionsIt may be inferred that the MAOA and MAOB variants may contribute to the etiology of ADHD in the Indo-Caucasoid population and could be responsible for higher occurrence of ADHD in the boys.
| S-EPMC5629801 | biostudies-literature
Project description:BackgroundIn different ethnic groups, birth related factors have shown significant influence in the etiology of Attention deficit hyperactivity disorder (ADHD). Based on these interesting findings, we aimed to investigate association between different pre- and post natal variables and ADHD associated traits in Indian subjects.MethodsADHD Probands recruited based on the DSM-IV, were assessed by the Conner's Parent Rating Scale for behavioral problem (BPr), inattention (IA), hyperactivity (HA) and ADHD index (AI). Impulsivity (Imp) was assessed by the Tsukuyama scale.ResultsHigher paternal (Std β = 0.23) and lower maternal (Std β = 0.21) age showed significant association with Imp of the probands. Higher paternal age also revealed association with BPr (Std β = 0.18). Age of onset was distinctly associated with AI (Std β < 0.16) while developmental delay was negatively correlated with BPr, Imp, IA and birth weight (r < - 0.13); also confirmed by Posthoc-ANOVA (P < 0.05).ConclusionWe infer that parental age, developmental delay and birth related variables may have a cumulative effect on ADHD symptom severity.
| S-EPMC6475966 | biostudies-literature
Project description:BACKGROUND:Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. METHODS:Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5?years, range 1.7 to 15.5?years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24?months using DSM-IV-TR criteria (n?=?89 concordant for ASD; n?=?296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24?months. RESULTS:Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ?=?1.06; 95% CI?=?1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC?=?0.50, p?<?0.001). CONCLUSIONS:Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24?months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.
| S-EPMC7003330 | biostudies-literature
Project description:BackgroundAttention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA) and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of monoamines and were explored for association with ADHD in different ethnic groups. In the present study, few exonic as well as intronic MAOB variants were analyzed in ADHD probands (N = 150) and ethnically matched controls (N = 150) recruited following the Diagnostic and Statistical Manual for Mental Disorders-4(th) edition (DSM-IV). Appropriate scales were used for measuring the behavioural attributes. Gene variants were analyzed by amplification of target sites followed by DNA sequencing and data obtained were analyzed by population based statistical methods.ResultsOut of 34 variants present in the analyzed sites, only seven functional variants, rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324 and rs3027440, were found to be polymorphic. rs2283728 'C' (P = 3.45e-006) and rs3027440 'T' (P = 0.02) alleles showed higher frequencies in ADHD probands as compared to controls. rs56220155 'A' (P = 0.04) allele and 'GA' (P = 0.04) genotype showed higher frequencies in the male and female ADHD probands respectively as compared to sex-matched controls. Analysis of pairwise linkage disequilibrium revealed striking differences between probands and controls. Haplotype analysis revealed significantly higher occurrence of different haplotypes in the ADHD probands while some haplotypes were detected in the controls only. Higher scores for conduct problems were found to be associated with rs56220155 'A' (P = 0.05) allele in the male ADHD probands. Multifactor dimensionality reduction analysis showed independent as well as interactive effects of polymorphic variants which were more robust in the male probands.ConclusionsSince all the polymorphic variants analyzed were functional, it may be inferred that MAOB gene variants are contributing to the etiology of ADHD in the Indo-Caucasoid population from eastern India which merits further in depth analysis.
| S-EPMC4921030 | biostudies-literature
Project description:The aim of the project was to explore the feasibility of gene expression profiles as a general diagnostic tool. Therefore the most frequently used and easy to use white blood cells have been profiled. We wanted to examinate, whether phenotypes created by organs different from blood cells have enough influence on these cells to allow the diagnosis of their presence. As a proof of principle we tried to identify surrogate markers for human sex (excluding markers on sex chromosomes). Keywords: indirect phenotype classification, surrogate marker classification, genetic differences
2006-08-12 | GSE3115 | GEO
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