Leveraging local identity-by-descent increases the power of case/control GWAS with related individuals

Large case/control Genome-Wide Association Studies (GWAS) often include groups of related individuals with known relationships. When testing for associations at a given locus, current methods incorporate only the familial relationships between individuals. Here, we introduce the chromosome-based Quasi Likelihood Score (cQLS) statistic that incorporates local Identity-By-Descent (IBD) to increase the power to detect associations. In studies robust to population stratification, such as those with case/control sibling pairs, simulations show that the study power can be increased by over 50%. In our example, a GWAS examining late-onset Alzheimer's disease, the $p$-values among the most strongly associated SNPs in the APOE gene tend to decrease, with the smallest $p$-value decreasing from $1.23\times10^{-8}$ to $7.70\times 10^{-9}$. Furthermore, as a part of our simulations, we reevaluate our expectations about the use of families in GWAS. We show that, although adding only half as many unique chromosomes, genotyping affected siblings is more efficient than genotyping randomly ascertained cases. We also show that genotyping cases with a family history of disease will be less beneficial when searching for SNPs with smaller effect sizes.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS715 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The clinical utility of testicular cancer risk loci

Three recent genome-wide association studies of testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1. The calculated per-allele odds ratio for variants in the region of KITLG is the highest reported for any malignancy so far. These findings are in agreement with epidemiological data indicating that testicular cancer has a higher heritability than most other cancers. Here, we discuss the question of whether the newly identified risk polymorphisms can be used to guide patient care

Diversity and Composition of the Adult Fecal Microbiome Associated with History of Cesarean Birth or Appendectomy: Analysis of the American Gut Project

AbstractBackgroundCesarean birth is associated with altered composition of the neonate's microbiota and with increased risk for obesity and other diseases later in life. The mechanisms of these associations, and whether cesarean birth is associated with an altered adult microbiota, are unknown.MethodsIn 1097 adult volunteers without diabetes, inflammatory bowel disease, or recent antibiotic use, fecal microbiome metrics were compared by history of cesarean birth (N=92) or appendectomy (N=115). Associations with potential confounders, microbiome alpha diversity, and individual microbial taxa were estimated by logistic regression. Permutation tests assessed differences in microbial composition (beta diversity) based on Jensen–Shannon divergence.FindingsCesarean birth history was associated with younger age; appendectomy with older age and higher body mass index. Neither was associated with fecal microbiome alpha diversity. Microbial composition at all taxonomic levels differed significantly with cesarean birth (P≤0.008) but not with appendectomy (P≥0.29). Relative abundance differed nominally for 17 taxa with cesarean birth and for 22 taxa with appendectomy, none of which was significant with adjustment for multiple comparisons.InterpretationAdults born by cesarean section appear to have a distinctly different composition of their fecal microbial population. Whether this distinction was acquired during birth, and whether it affects risk of disease during adulthood, are unknown.FundingSupported by the Intramural Research Program, National Cancer Institute, National Institutes of Health (Z01-CP-010214)

Badania nad poprawą wyników małych i mikroprzedsiębiorstw poprzez stosowanie zielonych innowacji

It is an important goal of China’s 2025 Strategy to build an environmental governance system with the government as the leading role, enterprises as the main body, and social organizations and the public all participate actively. In this context, whether and how small and micro enterprises, as a force of rejuvenating the country through science and technology, participate in the construction of environmental governance system is discussed in this paper. This study uses the 12th China small and micro enterprise survey database to deeply analyze the direct and indirect effects between green innovation and small and micro enterprise performance, and finds that: in the direct effect analysis, the direct promotion effect of green innovation on the financial performance of small and micro enterprises is related to the development stage of small and micro enterprises, which is significant in the initial stage and mature stage, but not significant in the growth stage; in the indirect effect analysis, green innovation can indirectly improve the overall performance of small and micro enterprises by improving their environmental and social responsibility performance. At the same time, green innovation can amplify the role of other factors in promoting the overall performance. This study not only enriches the research scope of green innovation theory from the subdivision dimension, provides a new perspective for the integration of green innovation and social responsibility theory, it also provides theoretical reference and guidance for the green innovation practice of small and micro enterprises.Ważnym celem chińskiej Strategii 2025 jest zbudowanie systemu zarządzania środowiskowego, z rządem odgrywającym wiodącą rolę, przedsiębiorstwami jako głównym organem  i aktywnie uczestniczącymi organizacjami społecznymi i społeczeństwem. W niniejszym artykule omówiono, czy i w jaki sposób małe i mikroprzedsiębiorstwa, uczestniczą w budowie systemu zarządzania środowiskiem. W badaniu wykorzystano 12. bazę danych ankietowych małych i mikroprzedsiębiorstw w Chinach, aby dogłębnie przeanalizować bezpośrednie i pośrednie zależności między zielonymi innowacjami a wynikami małych i mikroprzedsiębiorstw. Stwierdzono, że: w analizie skutków bezpośrednich bezpośredni wpływ promocji zielonych innowacji na finanse wyniki małych i mikroprzedsiębiorstw jest związany z fazą rozwoju małych i mikroprzedsiębiorstw, jest ona istotna w fazie początkowej i dojrzałej, ale nieistotna w fazie wzrostu; w analizie skutków pośrednich zielone innowacje mogą pośrednio poprawić ogólne wyniki małych i mikroprzedsiębiorstw poprzez poprawę ich wyników w zakresie odpowiedzialności środowiskowej i społecznej. Jednocześnie ekologiczne innowacje mogą wzmocnić rolę innych czynników w promowaniu ogólnej wydajności. Niniejszy artykuł nie tylko wzbogaca zakres badawczy teorii zielonych innowacji z wymiaru podpodziałowego, zapewnia nową perspektywę integracji zielonych innowacji i teorii odpowiedzialności społecznej, ale także dostarcza teoretycznego odniesienia i wskazówek dla praktyki zielonych innowacji małych i mikroprzedsiębiorstw

Research on “Promoting teaching by competition” in the construction of electronic majors in local colleges and universities

This paper aims at training practical electronic undergraduate talents in local ordinary undergraduate colleges and universities. Through analyzing the current situation and common construction methods of electronic major construction, this paper proposes to integrate electronic design competition into teaching design. In the practice process, the competition training and daily teaching depth integration, to achieve the purpose of promoting teaching by competition, and at the same time in practice summed up several integration models, the common planning method of promoting teaching by competition is put forward

Statistical corrections of linkage data suggest predominantly cis regulations of gene expression

Morley et al. (Nature 2004, 430:743–747) detected significant linkages to the expression levels of 142 genes (of 3554) at a reported threshold of genome-wide p = 0.001 (LOD ≈ 5.3), using 14 three-generation Centre d'Etude du Polymorphisme Humain pedigrees. Most of the linkages (77%) were trans, i.e., more than 5 Mb from the expressed gene. However, the analysis did not account for the expected anti-conservative effect of the skewed distribution of score- or regression-based statistics in large sibships, or for the possible variance distortion due to correlations among tests. Therefore, we re-analyzed their data, using a robust score statistic for the entire pedigrees and correcting the p-values for skewness. We found that a LOD of 5.3 had a skewness-corrected genome-wide p-value of 0.016 instead of 0.001 (a result that we confirmed using simulation), with around 50 expected false positives. We then further corrected for correlation among the (skew-corrected) p-values by using Efron's method for obtaining the empirical null distribution. Setting a threshold of FDR = 10% (Z = 6.4, LOD = 8.9), we detected linkage for the expression levels of 22 genes, 19 of which are cis. Limiting the analysis to cis regions, linkage was detected to the expression levels of 46 genes with 4.6 expected false positives (FDR = 10%)

Advances in Treatment of Nocturnal Enuresis in Children

Nocturnal enuresis is a condition with complex etiology affecting plenty of children and families. Even though multifarious clinical trials and studies have been designed and completed, some inconclusive results on nocturnal enuresis confuse clinicians. This article aims to provide useful information for clinicians by summarizing the existing evidence on nocturnal enuresis and discussing the effectiveness and safety of different treatments. Nocturnal enuresis mainly results from the disorders related to central nervous system, which may cause nocturnal polyuria, nighttime bladder capacity decline, arousal disorder, and various accompanying diseases. We discussed the efficacy and safety of different treatments for monosymptomatic nocturnal enuresis, including standard therapies, simple behavioral interventions, complex behavioral interventions, alarm therapy, desmopressin and other drugs, biofeedback therapy, electrical stimulation, acupuncture, Chinese herbal medicine, massage, and so on. Alarm is still the most effective single therapy with lower relapse rate. Desmopressin has efficacy mainly in children with nocturnal polyuria. Children with detrusor overactivity or decreasing functional bladder capacity can choose anticholinergics. Additionally, tricyclic drugs, biofeedback therapy, electrical stimulation, acupuncture, massage, and so on are therapeutic options for children with nocturnal enuresis

Secure Mobile Agents in Electronic Commerce by Using Undetachable Signatures from Pairings

It is expect that mobile agents technology will bring significant benefits to electronic commerce. But security issues, especially threats from malicious hosts, become a great obstacle of widespread deployment of applications in electronic commerce based on mobile agents technology. Undetachable digital signature is a category of digital signatures to secure mobile agents against malicious hosts. An undetachable signature scheme by using encrypted functions from bilinear pairings was proposed in this paper. The security of this scheme base on the computational intractability of discrete logarithm problem and computational Diffe-Hellman problem on gap Diffle-Hellman group. Furthermore, the scheme satisfies all the requirements of a strong non-designated proxy signature i.e. verifiability, strong unforgeability, strong identifiability, strong undeniability and preventions of misuse. An undetachable threshold signature scheme that enable the customer to provide n mobile agents with ‘shares’ of the undetachable signature function is also provided. It is able to provide more reliability than classical undetachable signatures