Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Investigations into the role of ampha-receptor mediated transmission in conditioned, psychostimulant influenced behaviours

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN023729 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Affects and Cognition in a Social Theory of Unconscious Processes

The final, definitive version of this article has been published in the Journal, Group Analysis, Vol 38 / Issue 1, 2005, Copyright The Group-Analytic Society , by SAGE Publications Ltd at : http://gaq.sagepub.com/This paper argues that affects and cognition cannot be separated in human consciousness and that human consciousness is fundamentally a social phenomenon. This contention is based on a number of arguments. First, research into brain functioning indicates that those centres of the brain that deal with emotion also deal with the capacity to select rational and moral actions. Second, is the argument that attachment and separation behaviours, that is, social acts, are essential for the human body’s capacity to regulate itself. Next, the paper reviews G. H. Mead’s theory of symbolic interactionism, according to which human consciousness and self consciousness arise in social acts so that the individual is social through and through. The notion of “the” unconscious is then explored. It is argued that this is a fundamentally individualistic notion of what is unconscious in human action and as such is incompatible with the contention that human consciousness is a social process. Suggestions are made for thinking of what is unconscious in terms of social processes. The paper concludes with a section on how one might think abut disturbance and pathology from the perspective of complex responsive processes.Peer reviewe