A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk

To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).     

A Nonparametric Approach to Cognitive Diagnosis by Proximity to Ideal Response Patterns

A trend in educational testing is to go beyond unidimensional scoring and provide a more complete profile of skills that have been mastered and those that have not. To achieve this, cognitive diagnosis models have been developed that can be viewed as restricted latent class models. Diagnosis of class membership is the statistical objective of these models. As an alternative to latent class modeling, a nonparametric procedure is introduced that only requires specification of an item-by-attribute association matrix, and classifies according to minimizing a distance measure between observed responses, and the ideal response for a given attribute profile that would be implied by the item-by-attribute association matrix. This procedure requires no statistical parameter estimation, and can be used on a sample size as small as 1. Heuristic arguments are given for why the nonparametric procedure should be effective under various possible cognitive diagnosis models for data generation. Simulation studies compare classification rates with parametric models, and consider a variety of distance measures, data generation models, and the effects of model misspecification. A real data example is provided with an analysis of agreement between the nonparametric method and parametric approaches.     

Mortality of the 'Golden Generation': what can the ONS Longitudinal study tell us?

It is well documented that the generations born around 1930 are consistently exhibiting higher rates of mortality improvement than the generations either side of them. There is currently no evidence that these differentials are declining. In current ONS National Population Projections, it is assumed that these cohorts will continue to experience higher rates of improvement. However, it is not yet precisely clear why this is so. This article details preliminary research carried out using the ONS Longitudinal Study to try to understand better why the members of the generation born around 1930 have been enjoying higher rates of mortality improvement throughout their adult life.     

Bolzano’s Infinite Quantities

In his Foundations of a General Theory of Manifolds, Georg Cantor praised Bernard Bolzano as a clear defender of actual infinity who had the courage to work with infinite numbers. At the same time, he sharply criticized the way Bolzano dealt with them. Cantor’s concept was based on the existence of a one-to-one correspondence, while Bolzano insisted on Euclid’s Axiom of the whole being greater than a part. Cantor’s set theory has eventually prevailed, and became a formal basis of contemporary mathematics, while Bolzano’s approach is generally considered a step in the wrong direction. In the present paper, we demonstrate that a fragment of Bolzano’s theory of infinite quantities retaining the part-whole principle can be extended to a consistent mathematical structure. It can be interpreted in several possible ways. We obtain either a linearly ordered ring of finite and infinitely great quantities, or a partially ordered ring containing infinitely small, finite and infinitely great quantities. These structures can be used as a basis of the infinitesimal calculus similarly as in non-standard analysis, whether in its full version employing ultrafilters due to Abraham Robinson, or in the recent “cheap version” avoiding ultrafilters due to Terence Tao.     

Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci

We carried out a meta-analysis of data from three genome-wide association (GWA) studies of type 1 diabetes (T1D), testing 305,090 SNPs in 3,561 T1D cases and 4,646 controls of European ancestry. We obtained further support for 4q27 (IL2-IL21, P = 1.9 x 10(-8)) and, after genotyping an additional 6,225 cases, 6,946 controls and 2,828 families, convincing evidence for four previously unknown and distinct risk loci in chromosome regions 6q15 (BACH2, P = 4.7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)).     

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.     

A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia

We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 x 10(-10)), 2q37.1 (rs13397985, SP140; P = 5.40 x 10(-10)), 6p25.3 (rs872071, IRF4; P = 1.91 x 10(-20)), 11q24.1 (rs735665; P = 3.78 x 10(-12)), 15q23 (rs7176508; P = 4.54 x 10(-12)) and 19q13.32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.     

Alkaloidal relationships in the genus Arctomecon (Papaveraceae) and herbivory in A. humilis

The previously reported alkaloids (including protopines, benzophenanthridines, tetrahydrobenzylisoquinolines, and protoberberines) of the genus Arctomecon (Papaveraceae) are discussed in relation to their distribution in the plant kingdom, in the Papaveraceae, and among the three species of Arctomecon . The biological activity of these alkaloids is discussed, and possible implications for herbivore and plant-insect interactions in A. humilis are presented.