Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

On the association between IPO underpricing and reversal and Taiwan's regulatory reforms for mandatory forecasts

The unique institutions in Taiwan may add to our understanding of the effect of initial public offering (IPO) firm disclosures. Consistent with the notion of market mispricing, most of Taiwan's IPOs were with consecutive up‐limit hits followed by substantial price reversals. In this study, we decompose IPO underpricing into two components: pure underpricing and subsequent reversal, exploring the impact of the 1991 mandate that IPO firms should include their management forecasts in the prospectuses on these two anomaly measures. Our results support the notion that disclosure regulations ameliorate investors' mispricing the stocks. First, pure underpricing and reversal are significantly less (more) pronounced for post‐mandate (pre‐mandate) IPO stocks. In contrast, consistent with the cheap talk hypothesis, the pre‐mandate voluntary forecasters (non‐forecasters) appear to be more (less) underpriced. Second, the duration of underpricing for the post‐mandate (pre‐mandate) IPOs appears to be shorter (longer). Nevertheless, underpricing lasted relatively longer (shorter) for the pre‐mandate IPOs with (with no) voluntary disclosures. Copyright © 2009 John Wiley & Sons, Ltd.     

Identification of ten loci associated with height highlights new biological pathways in human growth

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.     

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis

Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.     

A new insight into combining forecasts for elections: The role of social media

This study is devoted to gain insight into a timely, accurate, and relevant combining forecast by considering social media (Facebook), opinion polls, and prediction markets. We transformed each type of raw data into the possibility of victory as a forecasting model. Besides the four single forecasts, namely Facebook fans, Facebook “people talking about this” (PTAT) statistics, opinion polls, and prediction markets, we generated three combined forecasts by associating various combinations of the four components. Then, we examined the predictive performance of each forecast on vote shares and the elected/non‐elected outcome across the election period. Our findings, based on the evidence of Taiwan's 2018 county and city elections, showed that incorporating the Facebook PTAT statistic with polls and prediction markets generates the most powerful forecast. Moreover, we recognized the matter of the time horizons where the best proposed model has better accuracy gains in prediction—in the “late of election,” but not in “approaching election”. The patterns of the trend of accuracy across time for each forecasting model also differ from one another. We also highlighted the complementarity of various types of data in the paper because each forecast makes important contributions to forecasting elections.     

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta.     

Augmented Half‐Life Estimation Based on High‐Frequency Data

Half‐life estimation has been widely used to evaluate the speed of mean reversion for various economic and financial variables. However, half‐life estimation for the same variable are often different due to the length of the annual time series data used in alternative studies. To solve this issue, this paper extends the ARMA model and derives the half‐life estimation formula for high‐frequency monthly data. Our results indicate that half‐life estimation using short‐period monthly data is an effective approximation for that using long‐period annual data. Furthermore, by applying high‐frequency data, the required effective sample size can be reduced by at least 40% at the 95% confidence level. Copyright © 2015 John Wiley & Sons, Ltd.     

APPLICATION OF SURFACE WAVE METHOD TO HAZARD REDUCTION:A CASE STUDY IN HONG KONG

A case study in Hong Kong has demonstrated the potential application of the surface wave method to slope safety assessment. In the study, CSW measurements using frequency from 6 Hz to 100 Hz was conducted. The phase velocity results were inverted to obtain shear wave vdocity and shear modulus profiles. Subsequent geotechnicsl investigation provided drillhole data at two locations that were consistent with the inversion model results. The uppermost colluvium layer was found to be about 5 m thick at the two locations and has a shear modulus of 200 - 500 MPa.The method is quick, portable and non- invasive, and may be applied in terrain at where drilling is difficult.