A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia

Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4

Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

published_or_final_versio

Consumer Purchase Intention: An empirical study of consumer buying behaviour respect to Country of Origin, Brand Awareness, Brand Loyalty, Brand Image, and Perceived Quality.

Masteroppgave i International business and marketing (MSc

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia

Background Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15). Methods We conducted a large- scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10−6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23. Conclusions This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4

Supporting Licensed Science Teachers’ Professional Development in Adopting Learner-Centred Pedagogy in Tanzanian Secondary Schools

The purpose of this study was to obtain a better understanding of the professional learning needs of Tanzanian science teachers who were recruited using an alternative route approach to teacher recruitment and to seek ways to address these needs. The alternative route to teacher recruitment usually refers (but not always) to the enlistment of university graduates, who are trained in a non-accredited teacher education programme, and then licensed or certified to teach in schools. In Tanzania teachers trained in this way are referred to as ‘licensed teachers’. This study first identified the licensed teachers’ professional learning needs in relation to pedagogical content knowledge (PCK) by examining their effectiveness in using learner-centred teaching methods in the classroom. The findings from this first phase of the investigation revealed that the licensed science teachers rarely used learner-centred strategies and their PCK was underdeveloped in this area. In the second phase of the study a professional development intervention (PDI) was developed and implemented to enhance the licensed science teachers’ PCK and improve their classroom teaching practices. This study used a multiple case study approach underpinned by an interpretive research paradigm. The study adopted the situativity theory to inform the professional development intervention, with the view that teachers’ learning and knowing are situated in and influenced by the physical and social context and participation in authentic activity as a community of learners. The participants of this study were six licensed teachers, twenty four students and five education officials. Data were collected from multiple sources such as classroom observations, one-to-one semi-structured interviews, focus group discussions, documentary reviews and teachers’ reflective notes. The data were analysed thematically using the five components of PCK identified by Magnusson, Krajcik, and Borko (1999), as the analytical framework. The results from the first phase of investigation showed that the licensed science teachers had underdeveloped PCK and did not use/understand learner-centred teaching methods. Instead their classroom teaching practices were dominated by teacher-centred teaching methods and they lacked the skills of preparing learner-centred science lessons. Also tests and examinations prepared by the licensed science teachers were found to be mostly testing the lower levels of Bloom’s knowledge taxonomy, that is, knowledge, comprehension and application, with few items relating to analysis. The evaluation of the PDI indicated that it had a positive impact on licensed science teachers’ PCK, with the licensed teachers showing improved classroom teaching practices after the PDI. Students’ learning was enhanced as a direct result of licensed science teachers’ improvement in their ability to design and teach lesson using learner-centred teaching methods. This study has implications for teacher education practice and students’ learning in countries using an alternative approach to teacher recruitment and for educational research. This thesis offers suggestions for reform in teacher education institutions, policy and practice and for further research into how to improve this form of alternative route to teacher recruitment. The most significant of these suggestions is the setting up of PLCs of teachers with on-going expert support and school leadership (headmasters/mistresses, district educational officers) involvement. This on-site structure for sustained, supported professional learning offers a way forward for improving PCK of many untrained licensed teachers currently working in Tanzanian rural community secondary schools. The thesis concludes that unqualified licensed science teachers working in schools need school-based professional development support to enhance their underdeveloped PCK, since students taught by licensed teachers are unlikely to be receiving the levels of knowledge and skills potentially needed to compete in the global economy

The Lacuna in African Education Systems: Why the Systems are not Achieving the Needs for 21st Century Learned Citizens

This is a library–based research paper that explored problems facing African education systems in the 21st century and how to address these challenges. It is almost six decade since first African country received its independence from colonial masters  but African education systems are still ineffective and pupils are not in schools and those in schools some are graduating without  basic literacy skills of writing, reading and doing simple numeracy. The findings indicated that African education systems  has a lot structural problems such as policy issues, management problems, poor curriculum,  lack of funding  and l ‘political will’  to improve education system. This study  provide some suggestions on how to reform African education systems so as foster the skills development for the 21 century citizens