A three-stage approach for genome-wide association studies with family data for quantitative traits

Background: Genome-wide association (GWA) studies that use population-based association approaches may identify spurious associations in the presence of population admixture. In this paper, we propose a novel three-stage approach that is computationally efficient and robust to population admixture and more powerful than the family-based association test (FBAT) for GWA studies with family data. We propose a three-stage approach for GWA studies with family data. The first stage is to perform linear regression ignoring phenotypic correlations among family members. SNPs with a first stage p-value below a liberal cut-off (e.g. 0.1) are then analyzed in the second stage that employs a linear mixed effects (LME) model that accounts for within family correlations. Next, SNPs that reach genome-wide significance (e.g. $10^{-6}$ for 34,625 genotyped SNPs in this paper) are analyzed in the third stage using FBAT, with correction of multiple testing only for SNPs that enter the third stage. Simulations are performed to evaluate type I error and power of the proposed method compared to LME adjusting for 10 principal components (PC) of the genotype data. We also apply the three-stage approach to the GWA analyses of uric acid in Framingham Heart Study's SNP Health Association Resource (SHARe) project. Results: Our simulations show that whether or not population admixture is present, the three-stage approach has no inflated type I error. In terms of power, using LME adjusting PC is only slightly more powerful than the three-stage approach. When applied to the GWA analyses of uric acid in the SHARe project of FHS, the three-stage approach successfully identified and confirmed three SNPs previously reported as genome-wide significant signals. Conclusions: For GWA analyses of quantitative traits with family data, our three-stage approach provides another appealing solution to population admixture, in addition to LME adjusting for genetic PC

Scantegrity II Municipal Election at Takoma Park: The First E2E Binding Governmental Election with Ballot Privacy

On November 3, 2009, voters in Takoma Park, Maryland, cast ballots for the mayor and city council members using the Scantegrity II voting system—the first time any end-to-end (E2E) voting system with ballot privacy has been used in a binding governmental election. This case study describes the various efforts that went into the election—including the improved design and implementation of the voting system, streamlined procedures, agreements with the city, and assessments of the experiences of voters and poll workers. The election, with 1728 voters from six wards, involved paper ballots with invisible-ink confirmation codes, instant-runoff voting with write-ins, early and absentee (mail-in) voting, dual-language ballots, provisional ballots, privacy sleeves, any-which-way scanning with parallel conventional desktop scanners, end-to-end verifiability based on optional web-based voter verification of votes cast, a full hand recount, thresholded authorities, three independent outside auditors, fully-disclosed software, and exit surveys for voters and pollworkers. Despite some glitches, the use of Scantegrity II was a success, demonstrating that E2E cryptographic voting systems can be effectively used and accepted by the general public.United States. Dept. of Defense (IASP grant H98230-08-1-0334)United States. Dept. of Defense (IASP grant H98230-09-1-0404)National Science Foundation (U.S.) (Grant no. CNS 0831149

First-time mothers’ experiences of pregnancy and birth following assisted reproductive technology treatment in Taiwan

Background Assisted Reproductive Technology (ART) treatment tends to involve significant physical and emotional commitments that can impact maternal, infant and family health and well-being. An in-depth understanding of experiences is necessary to provide adequate support for women and their families during pregnancy and transition to parenthood following ART treatment. The aim of this study was to explore first-time mothers’ experiences of pregnancy and transition to parenthood following successful ART treatment in Taiwan. Method Twelve first-time mothers who conceived and gave live birth using ART treatment were purposively selected from a fertility centre in Taipei, Taiwan. Women’s experiences in pregnancy and in their transition to motherhood were explored using semi-structured in-depth interviews. All interviews were recorded, transcribed, and analysed using the Colaizzi strategy. Results The mothers’ accounts reflected three main themes: ‘being different from mothers who became pregnant naturally’; ‘ensuring health and safety of the foetus’; and ‘welcoming new lives with excitement’. The difference mothers felt about themselves was evident in four subthemes: becoming pregnant after a long wait, feeling vulnerable during pregnancy, relying on family’s assistance and support, and worrying about the impact of ART on health. The theme on ‘ensuring health and safety of the foetus’ encompassed three subthemes: activities to protect the unborn baby, monitoring foetal movement constantly to maintain peace of mind, and receiving foetal reduction for the sake of the pregnancy. Narratives around ‘welcoming new lives with excitement’ reflected four subthemes: overcoming hardship for worthwhile results, realising one’s life and dreams, proving to be fertile enough to give birth, and return to normal life track. Conclusion Findings indicate the need for educational and psychosocial interventions to support women and their families physically and psychologically during ART treatment. The stigma related to infertility and the psychosocial support from family are aspects to consider while planning intervention programmes

Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005

<p>Abstract</p> <p>Background</p> <p>The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population.</p> <p>Methods</p> <p>A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases.</p> <p>Results</p> <p>During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation,$504 for the elbow, $1,232 for the wrist,$1,103 for the hip, $1,888 for the knee, and$1,248 for the ankle.</p> <p>Conclusions</p> <p>In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture-dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure.</p

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4%) and Gly2385Arg variants (PAR ∼6%) yields a total PAR of ∼10%

T2 Values of Posterior Horns of Knee Menisci in Asymptomatic Subjects

[[abstract]]Purpose: The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects. Methods: Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20–34, 35–49 and 50–70 years. The inclusion criteria were BMI＜30 kg/cm2, normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T. Results: The mean T2 values in both medial and lateral menisci for the 20–34, 35–49, and 50–70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50–70 age group than the 20–34 age group (P＜0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50–70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50–70 and 35–49 age groups than that of the 20–34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P＜0.01). Conclusion: The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.[[incitationindex]]SCI[[booktype]]電子

Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase

Using spatial analysis to demonstrate the heterogeneity of the cardiovascular drug-prescribing pattern in Taiwan

<p>Abstract</p> <p>Background</p> <p>Geographic Information Systems (GIS) combined with spatial analytical methods could be helpful in examining patterns of drug use. Little attention has been paid to geographic variation of cardiovascular prescription use in Taiwan. The main objective was to use local spatial association statistics to test whether or not the cardiovascular medication-prescribing pattern is homogenous across 352 townships in Taiwan.</p> <p>Methods</p> <p>The statistical methods used were the global measures of Moran's <it>I </it>and Local Indicators of Spatial Association (LISA). While Moran's <it>I </it>provides information on the overall spatial distribution of the data, LISA provides information on types of spatial association at the local level. LISA statistics can also be used to identify influential locations in spatial association analysis. The major classes of prescription cardiovascular drugs were taken from Taiwan's National Health Insurance Research Database (NHIRD), which has a coverage rate of over 97%. The dosage of each prescription was converted into defined daily doses to measure the consumption of each class of drugs. Data were analyzed with ArcGIS and GeoDa at the township level.</p> <p>Results</p> <p>The LISA statistics showed an unusual use of cardiovascular medications in the southern townships with high local variation. Patterns of drug use also showed more low-low spatial clusters (cold spots) than high-high spatial clusters (hot spots), and those low-low associations were clustered in the rural areas.</p> <p>Conclusions</p> <p>The cardiovascular drug prescribing patterns were heterogeneous across Taiwan. In particular, a clear pattern of north-south disparity exists. Such spatial clustering helps prioritize the target areas that require better education concerning drug use.</p