Is GAD2 on chromosome 10p12 a potential candidate gene for morbid obesity?

Morbidly obese individuals represent one of the fastest growing subpopulations of obese individuals. Thus, it is of significant interest to broaden our understanding of the potential genetic causes of this public health concern. A recent study investigated a role of positional candidate gene GAD2 (the gene for glutamic acid decarboxylase) in the development of morbid obesity.

A locus for generalized tonic-clonic seizure susceptibility maps to chromosome 10q25-q26.

Inheritance patterns in twins and multiplex families led us to hypothesize that two loci were segregating in subjects with juvenile myoclonic epilepsy (JME), one predisposing to generalized tonic-clonic seizures (GTCS) and a second to myoclonic seizures. We tested this hypothesis by performing genome-wide scan of a large family (Family 01) and used the results to guide analyses of additional families. A locus was identified in Family 01 that was linked to GTCS (10q25-q26).

New joint covariance- and marginal-based tests for association and linkage for quantitative traits for random and non-random sampling.

We develop novel statistical tests for transmission disequilibrium testing (tests of linkage in the presence of association) for quantitative traits using parents and offspring. These joint tests utilize information in both the covariance (or more generally, dependency) between genotype and phenotype and the marginal distribution of genotype. Using computer simulation we test the validity (Type I error rate control) and power of the proposed methods, for additive, dominant, and recessive modes of inheritance, locus-specific heritability of the trait 0.

The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept.

Objective: To examine the roles of specific genetic polymorphisms as predictors of response to treatment of early rheumatoid arthritis (RA).

Methods: Subjects included 457 patients with early RA (duration of < or =3 years) who participated in a randomized controlled trial comparing weekly methotrexate and 2 dosages of etanercept (10 mg twice weekly and 25 mg twice weekly). Our primary outcome measure was achievement of 50% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR50 response) after 12 months of treatment.

Structural equation model-based genome scan for the metabolic syndrome.

Background: The metabolic syndrome is characterized by the clustering of several traits, including obesity, hypertension, decreased levels of HDL cholesterol, and increased levels of glucose and triglycerides. Because these traits cluster, there are likely common genetic factors involved.

Results: We used a multivariate structural equation model (SEM) approach to scan the genome for loci involved in the metabolic syndrome.

Do allelic variants of SLC6A14 predispose to obesity?

Obesity is arguably the world's most prevalent nutritional disorder and is a substantial contributor to morbidity and early mortality. Obesity is known to have a strong genetic component, but the specific influential genes in humans are largely unknown. A new paper describes a genetic variant that appears as though it may cause some people to be fatter or thinner than others (see the related article beginning on page 1762).

X-linked extension of the revised Haseman-Elston algorithm for linkage analysis in sib pairs.

Haseman and Elston (H-E) proposed a regression-based robust test of linkage between a marker and an autosomal quantitative trait locus, using the squared sib pair trait difference as a dependent variable and the proportion of alleles shared identical by descent by the sib pair as an independent variable. Several authors have proposed improvement of the original H-E's seminal work by using an optimal linear combination of squared sum and squared difference as the dependent variable. In this paper, we extend Haseman and Elston's sib pair method to an X-linked locus.

Heritability analysis of cytokines as intermediate phenotypes of tuberculosis.

Numerous studies have provided support for genetic susceptibility to tuberculosis (TB); however, heterogeneity in disease expression has hampered previous genetic studies. The purpose of this work was to investigate possible intermediate phenotypes for TB. A set of cytokine profiles, including antigen-stimulated whole-blood assays for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and the ratio of IFN to TNF, were analyzed in 177 pedigrees from a community in Uganda with a high prevalence of TB.

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation.

A genome-wide linkage analysis investigating the determinants of blood pressure in whites and African Americans.

Evidence for genomic regions influencing systolic and diastolic blood pressure (BP) were assessed in a whole genome linkage analysis in 211 African American and 160 white families as part of the GenNet network of the National Heart, Lung and Blood Institute-sponsored Family Blood Pressure Program. Multipoint regression and variance components linkage methods were used to analyze 372 polymorphic markers. Statistically compelling evidence for linkage (P values .

Familial correlations and heritability of maxillary midline diastema.

The purpose of the study was to estimate familial correlations and heritability to evaluate familial aggregation patterns of maxillary midline diastemas. The sample consisted of 30 extended families: 15 black, 14 white, and 1 mixed race. A single ascertainment scheme was adopted to collect the sample.