Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al.

Familiar characteristics and received familiar support among Brazilian adolescents with and without pregnancy experience

The present paper aimed to investigate how adolescents with pregnancy experience evaluate received support from their families in comparison with an adolescent group without pregnancy experience. 452 low income adolescents, both sex, aged 14 to 19 years old answered to a questionnaire. The results revealed that more girls (64.2 %) than boys (35.8 %) declared pregnancy experience, ?2 (2, n = 2617) = 48.32, p < .001. Moreover, it was observed that the group with pregnancy experience, in comparison with other group, revealed more perception on the family relationships safety, t (408) = -3.0, p < .01; mutual respect among family members in their homes, t (392) = -2.3, p < .05; and received stronger general support from their family, t (397) = -1,3, p < .05. These results are discussed.

Reliability of the Brief Neuropsychological Assessment Instrument Neupsilin

This study aimed to evaluate the reliability of Neupsilin Brief Neuropsychological Assessment Instrument, a brief battery developed in Brazil. Hundred two Brazilian man and women participated, from 18 to 40 years of age. It was evaluated the test-retest reliability of the Neupsilin tasks and the reliability of the correction of the constructional praxis task by different evaluators. The data were analyzed by Spearman’s correlation, intraclass correlation and Cronbach’s alpha. Language, memory, praxis and executive functions presented the highest correlations in the test-retest analyses. The agreement in the correction of the constructional praxis task was moderate to high. The results indicate temporal reliability of Neupsilin tasks and inter-rater agreement in the correction of the constructional praxis task. Suggestions to improve the tasks, the validity and reliability of Neupsilin were presented.