A Sib-Pair analysis of impulsivity in bipolar disorder type I

OBJECTIVE: The aim of this study was to compare impulsivity among patients with bipolar disorder, their siblings, and healthy controls in order to examine whether impulsivity in bipolar disorder is related to genetic liability for the illness. METHODS: Using the Barratt Impulsiveness Scale, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without bipolar disorder, and 70 healthy controls. RESULTS: Impulsivity scores were higher among patients with bipolar disorder than among healthy controls. Siblings showed higher motor impulsivity scores than did healthy controls. CONCLUSIONS: Our results suggest that motor impulsivity may be a vulnerability marker for bipolar disorder. Our data may contribute to further improve preventive strategies in subjects at high risk for bipolar disorder.

THE ROLE OF AN EXPLICIT CAUSAL FRAMEWORK IN AFFECTED SIB PAIR DESIGNS WITH COVARIATES

The affected sib/relative pair (ASP/ARP) design is often used with covariates to find genes that can cause a disease in pathways other than through those covariates. However, such "covariates" can themselves have genetic determinants, and the validity of existing methods has so far only been argued under implicit assumptions. We propose an explicit causal formulation of the problem using potential outcomes and principal stratification. The general role of this formulation is to identify and separate the meaning of the different assumptions that can provide valid causal inference in linkage analysis. This separation helps to (a) develop better methods under explicit assumptions, and (b) show the different ways in which these assumptions can fail, which is necessary for developing further specific designs to test these assumptions and confirm or improve the inference. Using this formulation in the specific problem above, we show that, when the "covariate" (e.g., addiction to smoking) also has genetic determinants, then existing methods, including those previously thought as valid, can declare linkage between the disease and marker loci even when no such linkage exists. We also introduce design strategies to address the problem.

Neoadjuvant hormone therapy for radical prostate radiotherapy:bicalutamide monotherapy vs. luteinizing hormone-releasing hormone agonist monotherapy: a single-institution matched-pair analysis

The purpose of this study was to compare the prostate-specific antigen (PSA) response to either neoadjuvant bicalutamide (BC) monotherapy or neoadjuvant luteinizing hormone-releasing hormone agonist (LHRHa) monotherapy and the subsequent effect on biochemical failure-free survival (BFFS) in men receiving radical radiotherapy (RT) for localized prostate cancer.

Quantitative fractography by digital image processing: NIH Image macro tools for stereo pair analysis and 3-D reconstruction

A set of NIH Image macro programs was developed to make qualitative and quantitative analyses from digital stereo pictures produced by scanning electron microscopes. These tools were designed for image alignment, anaglyph representation, animation, reconstruction of true elevation surfaces, reconstruction of elevation profiles, true-scale elevation mapping and, for the quantitative approach, surface area and roughness calculations. Limitations on time processing, scanning techniques and programming concepts are also discussed.

Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: a matched-pair analysis

To investigate the serum level distribution of angiogenic markers (PlGF, endoglin, sFlt-1) and acute-phase proteins (SAA, CRP) in patients with HELLP syndrome or preeclampsia (PE) including matched controls.

Matched-pair analysis of endovascular versus open surgical repair of abdominal aortic aneurysms in young patients at low risk

PURPOSE: To compare clinical outcomes of endovascular and open aortic repair of abdominal aortic aneurysms (AAAs) in young patients at low risk. It was hypothesized that endovascular aneurysm repair (EVAR) compares favorably with open aneurysm repair (OAR) in these patients. MATERIALS AND METHODS: Twenty-five patients aged 65 years or younger with a low perioperative surgical risk profile underwent EVAR at a single institution between April 1994 and May 2007 (23 men; mean age, 62 years+/-2.8). A sex- and risk-matched control group of 25 consecutive patients aged 65 years or younger who underwent OAR was used as a control group (23 men; mean age, 59 years+/-3.9). Patient outcomes and complications were classified according to Society of Vascular Surgery/International Society for Cardiovascular Surgery reporting standards. RESULTS: Mean follow-up times were 7.1 years+/-3.2 after EVAR and 5.9 years+/-1.8 after OAR (P=.1020). Total complication rates were 20% after EVAR and 52% after OAR (P=.0378), and all complications were mild or moderate. Mean intensive care unit times were 0.2 days+/-0.4 after EVAR and 1.1 days+/-0.4 after OAR (P<.0001) and mean lengths of hospital stay were 2.3 days+/-1.0 after EVAR and 5.0 days+/-2.1 after OAR (P<.0001). Cumulative rates of long-term patient survival did not differ between EVAR and OAR (P=.144). No AAA-related deaths or aortoiliac ruptures occurred during follow-up for EVAR and OAR. In addition, no surgical conversions were necessary in EVAR recipients. Cumulative rates of freedom from secondary procedures were not significantly different between the EVAR and OAR groups (P=.418). Within a multivariable Cox proportional-hazards analysis adjusted for patient age, maximum AAA diameter, and cardiac risk score, all-cause mortality rates (odds ratio [OR], 0.125; 95% CI, 0.010-1.493; P=.100) and need for secondary procedures (OR, 5.014; 95% CI, 0.325-77.410; P=.537) were not different between EVAR and OAR. CONCLUSIONS: Results from this observational study indicate that EVAR offers a favorable alternative to OAR in young patients at low risk.

A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families

Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disease characterized by the production of pathogenic autoantibodies. Previous genetic studies have suggested associations with HLA Class II alleles, complement gene deficiencies, and Fc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesis. Here, we report the results of a genome-wide microsatellite marker screen in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) [D6S257, logarithm of odds (lod) = 3.90, P = 0.000011] and at three additional regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21–23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Another nine regions (1p36, 1p13, 1q42, 2p15, 2q21–33, 3cent-q11, 4q28, 11p15, and 15q26) were identified with lod scores ≥1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.

Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci

After ingestion of a standardized dose of ethanol, alcohol concentrations were assessed, over 3.5 hours from blood (six readings) and breath (10 readings) in a sample of 412 MZ and DZ twins who took part in an Alcohol Challenge Twin Study (ACTS). Nearly all participants were subsequently genotyped on two polymorphic SNPs in the ADH1B and ADH1C loci known to affect in vitro ADH activity. In the DZ pairs, 14 microsatellite markers covering a 20.5 cM region on chromosome 4 that includes the ADH gene family were assessed, Variation in the timed series of autocorrelated blood and breath alcohol readings was studied using a bivariate simplex design. The contribution of a quantitative trait locus (QTL) or QTL's linked to the ADH region was estimated via a mixture of likelihoods weighted by identity-by-descent probabilities. The effects of allelic substitution at the ADH1B and ADH1C loci were estimated in the means part of the model simultaneously with the effects sex and age. There was a major contribution to variance in alcohol metabolism due to a QTL which accounted for about 64% of the additive genetic covariation common to both blood and breath alcohol readings at the first time point. No effects of the ADH1B*47His or ADH1C*349Ile alleles on in vivo metabolism were observed, although these have been shown to have major effects in vitro. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by these polymorphisms. Earlier analyses of these data suggested that alcohol metabolism is related to drinking behavior and imply that this QTL may be protective against alcohol dependence.

Use of the EM algorithm to detect QTL affecting multiple-traits in an across half-sib family analysis

QTL detection experiments in livestock species commonly use the half-sib design. Each male is mated to a number of females, each female producing a limited number of progeny. Analysis consists of attempting to detect associations between phenotype and genotype measured on the progeny. When family sizes are limiting experimenters may wish to incorporate as much information as possible into a single analysis. However, combining information across sires is problematic because of incomplete linkage disequilibrium between the markers and the QTL in the population. This study describes formulae for obtaining MLEs via the expectation maximization (EM) algorithm for use in a multiple-trait, multiple-family analysis. A model specifying a QTL with only two alleles, and a common within sire error variance is assumed. Compared to single-family analyses, power can be improved up to fourfold with multi-family analyses. The accuracy and precision of QTL location estimates are also substantially improved. With small family sizes, the multi-family, multi-trait analyses reduce substantially, but not totally remove, biases in QTL effect estimates. In situations where multiple QTL alleles are segregating the multi-family analysis will average out the effects of the different QTL alleles.

Evaluating small business performance : a matched pair analysis of African Caribbean owned businesses in the UK

African Caribbean Owned Businesses (ACOBs) have been postulated as having performance-related problems especially when compared with other ethnic minority groups in Britain. This research investigates if ACOBs may be performing less than similar firms in the population and why this maybe so. Therefore the aspiration behind this study is one of ratifying the existence of performance differentials between ACOBs and White Asian Owned Businesses (WAOBs), by using a triangulation of methods and matched pair analysis. Every ACOB was matched along firm specific characteristics of age, size, legal form and industry (sector), with similar WAOBs. Findings show support for the hypothesis that ACOBs are more likely to perform less than the WAOBs; WAOBs out-performed ACOBs in the objective and subjective assessments. Though we found some differentials between both groups in the entrepreneur’s characteristics and various emphases in strategic orientation in overall business strategy. The most likely drivers of performance differentials were found in firm activities and operations. ACOBs tended to have brands that were not as popular in the mainstream with most of their manufactured goods being seen as ‘exotic’ while those by WAOBs were perceived as ‘traditional’. Moreover, ACOBs had a higher proportion of clients constituting of individuals than business organisations while the WAOBs had a higher proportion consisting of business organisations.

Molecular genetic analyses of RFLPs for PCR-amplified growth hormone gene, renal kallikrein gene and atrial natriuretic factor gene in essential hypertension

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (χ1=0.34, P=0.55); (ii) a TaqI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (χ2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (χ2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension.