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Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.

ABSTRACT: Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.

SUBMITTER: Desrivieres S

PROVIDER: S-EPMC4051592 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cortical thickness and folding deficits in conduct-disordered adolescents.

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A Study of Predictive Ability of the Epigenetic Patterns in Peripheral Tissue for the Cortical Thickness

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A Single Nucleotide C3 Polymorphism Associates With Clinical Outcome After Lung Transplantation.

Project description:Background: Development of chronic rejection is still a severe problem and causes high mortality rates after lung transplantation (LTx). Complement activation is important in the development of acute rejection (AR) and bronchiolitis obliterans syndrome, with C3 as a key complement factor. Methods: We investigated a single nucleotide polymorphism (SNP) in the C3 gene (rs2230199) in relation to long-term outcome after LTx in 144 patient-donor pairs. In addition, we looked at local production of donor C3 by analyzing bronchoalveolar lavage fluid (BALF) of 6 LTx patients using isoelectric focusing (IEF). Results: We demonstrated the presence of C3 in BALF and showed that this is produced by the donor lung based on the genotype of SNP rs2230199. We also analyzed donor and patient SNP configurations and observed a significant association between the SNP configuration in patients and episodes of AR during 4-years follow-up. Survival analysis showed a lower AR-free survival in homozygous C3 slow patients (p = 0.005). Furthermore, we found a significant association between the SNP configuration in donors and BOS development. Patients receiving a graft from a donor with at least one C3 fast variant for rs2230199 had an inferior BOS-free survival (p = 0.044). Conclusions: In conclusion, our data indicate local C3 production by donor lung cells. In addition, a single C3 SNP present in recipients affects short-term outcome after LTx, while this SNP in donors has an opposite effect on long-term outcome after LTx. These results could contribute to an improved risk stratification after transplantation.

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Cortical Thickness in Adolescents with a Family History of Alcohol Use Disorder.

Project description:BACKGROUND:Individuals with a family history (FH+) of alcohol use disorder (AUD) have a higher risk for developing an AUD than those with no family history (FH-) of AUD. In addition, FH+ individuals tend to perform worse on neuropsychological measures and show heightened impulsivity, which may be due to underlying differences in brain structure such as cortical thickness. The primary aim of this study was to investigate differences in cortical thickness in FH+ compared to FH- adolescents. Secondary aims were to (i) investigate differences in executive functioning and impulsivity, and (ii) examine associations between brain structure and behavior. METHODS:Brain scans of 95 FH- and 93 FH+ subjects aged 13 to 18 were obtained using magnetic resonance imaging. FH+ subjects were required to have at least 1 biological parent with a history of an AUD. FH+ and FH- individuals had limited or no past alcohol use, thereby minimizing potential effects of alcohol. Subjects were evaluated on impulsivity and executive functioning tasks. Thicknesses of cortical lobes and subregions were analyzed using FreeSurfer. Regions showing group differences were examined for group-by-age interactions and correlations with neuropsychological and personality measures. RESULTS:FH+ adolescents had thinner cortices in frontal and parietal lobes, notably in the medial orbitofrontal, lateral orbitofrontal, and superior parietal cortices. The difference in cortical thickness between family history groups was strongest among the youngest subjects. FH+ subjects were also more impulsive and had poorer performance on a spatial memory task. CONCLUSIONS:These findings demonstrate frontal and parietal structural differences in FH+ adolescents that might underlie cognitive and behavioral characteristics associated with AUD risk.

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SHBG gene polymorphism (rs1799941) associates with metabolic syndrome in children and adolescents.

Project description:BackgroundMetabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.MethodsGenetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls).ResultsLogistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).ConclusionsThe significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

| S-EPMC4380117 | biostudies-literature

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