Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

© 2018, The Author(s). Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.status: publishe

Potential early-life predictors of dietary behaviour in adulthood: a retrospective study

This paper is in closed access.OBJECTIVE: Unnecessary dietary restraint (ie in the absence of a need to lose weight) and chronic overeating are both very unhealthy activities. As a precursor to a more involved longitudinal study, we sought to identify potential early-life predictors that merit scrutiny in this context. DESIGN: Four retrospective questionnaire studies were conducted (Study 1, N¼242; Study 2, N¼297; Study 3, N¼175; Study 4, N¼261). Female participants (18–30 y) completed measures of current dietary restraint and overeating. They also recalled experiences between 5 and 10 years of age. All were staff or students at Loughborough University (UK). RESULTS: After considering obvious sources of systematic bias, we report evidence that (i) dietary restraint is related to memories of maternal weight and dietary behaviour, and (ii) overeating and meal-size selection are both associated with memories of receiving a high-energy diet. CONCLUSION: The role of maternal factors in dietary restraint is consistent with previous research exploring the early onset of this behaviour. However, the relationship between childhood diet and overeating has not been suggested elsewhere. This is particularly important because it suggests a previously unreported correspondence between childhood experience and behaviours associated with obesity in adulthood