Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.

Bullying Involvement and Adolescent Substance Use: A Study of Multilevel Risk and Protective Factors

Thesis (Master, Psychology) -- Queen's University, 2016-08-02 13:18:40.65

Association entre l’environnement social en milieu de garde et les comportements liés à l’apport alimentaire et l'activité physique des enfants de trois à cinq ans

Résumé : Problématique : Puisque les enfants de moins de cinq ans passent environ 29 heures par semaine dans les milieux de garde et qu’ils apprennent en observant et en imitant les autres, les éducateurs et les pairs peuvent être des modèles importants dans l’apprentissage de saines habitudes de vie. Les objectifs étaient d’analyser les associations entre 1) les pratiques des éducateurs et l’apport alimentaire, 2) l’activité physique (AP) des enfants de trois à cinq ans dans les milieux de garde, 3) le degré d’influence des pairs sur l’apport alimentaire, et 4) l’AP des enfants de trois à cinq ans. Méthodes : Les associations entre les pratiques des éducateurs et les comportements liés à l’apport alimentaire et l’AP des enfants ont été étudiées à l’aide d’une étude transversale, menée auprès de 723 enfants de trois à cinq ans de 51 milieux de garde en Saskatchewan et au Nouveau-Brunswick à l’automne 2013 et 2014. Le degré d’influence des pairs sur l’apport alimentaire et l’AP des enfants a été étudié à l’aide d’une étude longitudinale, menée auprès de 238 enfants de trois à cinq ans au début et à la fin des années scolaires 2013-2014 et 2014-2015. L’AP des enfants a été mesurée à l’aide d’accéléromètres, et l’apport alimentaire a été mesuré à l’aide d’une analyse de consommation par pesée et photographiée. Une grille d’observation de l’environnement a permis de mesurer les pratiques des éducateurs en milieu de garde. Des régressions linéaires multiniveaux ont répondu aux quatre objectifs de l’étude. Résultats : Le modelage est positivement associé à l’apport en sucre (p=0,026) et l’éducation alimentaire est négativement associée à l’apport en calories (p=0,026) et en fibres (p=0,044). Ne pas utiliser de récompenses alimentaires est négativement associée à l’apport en gras (p=0,049). Aucune pratique n’est associée à l’AP des enfants. Plus l’écart entre l’apport alimentaire et l’AP des enfants et ceux de leurs pairs est grand au début de l’année, plus les enfants voient leur apport alimentaire et leur AP changer, se rapprochant de la moyenne de leurs pairs neuf mois plus tard (p<0,05). Conclusion : Les éducateurs et les pairs jouent un rôle important dans l’adoption d’habitudes alimentaires saines et d’AP chez les enfants de trois à cinq ans dans les milieux de garde. L’environnement social est donc important à considérer dans les interventions de promotion d’habitudes de vie saine dans les milieux de garde.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.

The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and its Association with Quality of Life in Ambulatory Patients Receiving Radiotherapy

OBJECTIVE: To evaluate the scored Patient-generated Subjective Global Assessment (PG-SGA) tool as an outcome measure in clinical nutrition practice and determine its association with quality of life (QoL). DESIGN: A prospective 4 week study assessing the nutritional status and QoL of ambulatory patients receiving radiation therapy to the head, neck, rectal or abdominal area. SETTING: Australian radiation oncology facilities. SUBJECTS: Sixty cancer patients aged 24-85 y. INTERVENTION: Scored PG-SGA questionnaire, subjective global assessment (SGA), QoL (EORTC QLQ-C30 version 3). RESULTS: According to SGA, 65.0% (39) of subjects were well-nourished, 28.3% (17) moderately or suspected of being malnourished and 6.7% (4) severely malnourished. PG-SGA score and global QoL were correlated (r=-0.66, P<0.001) at baseline. There was a decrease in nutritional status according to PG-SGA score (P<0.001) and SGA (P<0.001); and a decrease in global QoL (P<0.001) after 4 weeks of radiotherapy. There was a linear trend for change in PG-SGA score (P<0.001) and change in global QoL (P=0.003) between those patients who improved (5%) maintained (56.7%) or deteriorated (33.3%) in nutritional status according to SGA. There was a correlation between change in PG-SGA score and change in QoL after 4 weeks of radiotherapy (r=-0.55, P<0.001). Regression analysis determined that 26% of the variation of change in QoL was explained by change in PG-SGA (P=0.001). CONCLUSION: The scored PG-SGA is a nutrition assessment tool that identifies malnutrition in ambulatory oncology patients receiving radiotherapy and can be used to predict the magnitude of change in QoL.