Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Canadian immigrants at the polls: The effects of socialisation in the country of origin and resocialisation in Canada on electoral participation

Political socialisation plays a crucial but complex role in determining how immigrants adjust to the political environment of their host country. This study examines the effects of initial political socialisation and resocialisation on immigrants’ electoral participation in Canada. It addresses three questions: To what extent does the outlooks that develop from earlier political experiences in the country of origin shape immigrants’ subsequent electoral participation in Canada? To what extent, and how, does subsequent experience with politics in Canada affect electoral participation? And finally, how does initial socialisation in the country of origin condition resocialisation in Canada? The results indicate that not only does resocialisation leave a unique and lasting imprint on immigrant electoral participation in the host country, but also that the nature of resocialisation process in the host country is conditioned by the distinctive political outlooks immigrants acquire under different political regimes in their respective countries of origin

Trust among recent immigrants in Canada: levels, roots and implications for immigrant integration

Generalised trust promotes social interactions and may well be a crucial component of immigrant integration. Recent immigrants in particular are likely to be viewed by themselves and others as ‘outsiders’ who are unfamiliar with the expectations and norms that structure day-to-day social interactions in the host country. This study relies on a unique combination of three sources of data all derived from World Values Surveys to examine levels of trust, and its sources, among newcomers in one country with a large immigrant population, Canada. The evidence indicates that recent immigrants to Canada make a clear distinction between trust in other people in general, and trust in Canadians in particular: the former is grounded in pre-migration cultural influences, while the latter is grounded in immigrants’ experiences in the new host country. Moreover, the evidence suggests trust in Canadians is a crucial component of immigrant integration

Earning their support: feelings towards Canada among recent immigrants

This article examines the factors that lie behind Canada's success at earning the support of its newcomers. It examines the extent to which feelings towards Canada are grounded in immigrants' experiences in the host country, predispositions inherited from their lives prior to migration, and their comparative assessments of the host country and the country of origin. The findings indicate that although feelings towards Canada are partly shaped by post-migration factors, immigrants also interpret experiences in their new host country through the lens of their pre-migration experiences