Association Study of Common Mitochondrial Variants and Cognitive Ability

Abstract Mitochondria are central to optimal functioning of the nervous system and disruption of mitochondrial function is known to lead to cognitive impairment. However, there has been little focus on whether common mitochondrial DNA polymorphisms contribute to normal variation in cognitive phenotypes. In this study, we use methodology for carrying out whole mitochondrial association studies in family cohorts to test whether 69 common mitochondrial variants and 10 common European haplogroups are associated with a number of measures of cognition, including information processing, word recognition and general cognitive ability, in a sample of Australian adolescent twins and their singleton/non-twin siblings. With data from 1,385 individuals from 665 families, this is by far the largest mitochondrial association study of cognition undertaken to date. We find that there is no significant evidence that either common European mitochondrial SNPs or haplogroups are associated with variation in cognitive performance. In spite of the associations not reaching significance, several of the most highly associated SNPs are in mitochondrial genes that have previously been identified as potentially playing a role in cognitive performance in mice. These genes warrant further investigation in both functional and association studies with larger cohorts

Discordance of Tuberculin Skin Test and Interferon Gamma Release Assay in Recently Exposed Household Contacts of Pulmonary TB Cases in Brazil

Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion