A role for the MEGF6 gene in predisposition to osteoporosis.

Osteoporosis is a common skeletal disorder characterized by deterioration of bone tissue. The set of genetic factors contributing to osteoporosis is not completely specified. High-risk osteoporosis pedigrees were analyzed to identify genes that may confer susceptibility to disease. Candidate predisposition variants were identified initially by whole exome sequencing of affected-relative pairs, approximately cousins, from 10 pedigrees. Variants were filtered on the basis of population frequency, concordance between pairs of cousins, affecting a gene associated with osteoporosis, and likelihood to have functionally damaging, pathogenic consequences. Subsequently, variants were tested for segregation in 68 additional relatives of the index carriers. A rare variant in MEGF6 (rs755467862) showed strong evidence of segregation with the disease phenotype. Predicted protein folding indicated the variant (Cys200Tyr) may disrupt structure of an EGF-like calcium-binding domain of MEGF6. Functional analyses demonstrated that complete loss of the paralogous genes megf6a and megf6b in zebrafish resulted in significant delay of cartilage and bone formation. Segregation analyses, in silico protein structure modeling, and functional assays support a role for MEGF6 in predisposition to osteoporosis.

Disparities in children's use of oral health services.

OBJECTIVES: We sought to determine if the recent expansions in Medicaid and the State Children's Health Insurance Program (SCHIP) have resulted in a narrowing of income disparities over time with the use of dental care in children 2 to 17 years of age. METHODS: Six years of data from the National Health Interview Survey were utilized. A trend analysis was conducted using 1983 as a baseline, which predates the expansions, and 2001-2002, the endpoint, which postdates implementation of the expansions. In addition, we examined two intermediate time points (1989 and 1997-1998). We conducted unadjusted and adjusted analyses using logistic regression. RESULTS: Overall, use of ambulatory dental care has increased dramatically for children over the past two decades. In 1983, more than one in three children (38.5%) had no dental care within the previous 12 months. By 2001-2002, about one-quarter of children (26.3%) were reported to have no dental care within the year, a reduction of 12.2% from 1983 (p<0.001). Frequency of unmet dental care remained unchanged between 1997-1998 (the first year this measure was available) and 2001-2002. A reduction in income disparities for use of dental care was found in our unadjusted analysis but this difference became statistically insignificant in the adjusted analysis. No changes in income disparities occurred for unmet dental needs in either the unadjusted or adjusted analyses. CONCLUSIONS: A substantial overall improvement in dental care use has occurred among all income groups, including poor and near poor children. This "keeping up" with their higher-income counterparts represents an important public health accomplishment for children in low-income families. Nevertheless, additional efforts are needed to close remaining disparities in access to dental care.

Universal health care coverage for children: impact on pediatric health care providers.

A Northern California county expanded health coverage to cover nearly all children in the state through a new insurance program. In two years, 75,500 children entered a health care system near capacity. We hypothesized that the influx of thousands of previously uninsured children into the health system would affect providers in many ways. This cross-sectional study sought to investigate how this influx affected provider practices, job satisfaction, access to specialists, and overarching views about the program. Qualitative analyses of expert interviews were performed. Providers reported improved access to health care, specialists, and medications for patients. They cited increased job satisfaction for providers due to fewer limits on care, improved referral process, and decreased patient family financial stress. Providers noted the persistence of long appointment wait times for specialist care. After moving to near universal coverage, safety net providers described increased job satisfaction. Because this study examined safety-net providers, future research requires a more representative sample of providers.

The impact of public insurance expansions on children's access and use of care.

OBJECTIVE: Our goal was to examine the impact of the State Children's Health Insurance Program nationally on children's access and use of health care. OBJECTIVE: Our data source was the National Health Interview Survey, using 1997 as a baseline, which predates the implementation of the State Children's Health Insurance Program, and 2003 as the end point of the analysis. We analyzed 25,734 children aged 0 to 18 years (1997 and 2003 combined) to examine changes in health insurance coverage rates, health care access, and utilization for children in the State Children's Health Insurance Program target population, defined here as those living in families with incomes between 100% and 199% of the federal poverty level. RESULTS: Children in the State Children's Health Insurance Program target income group showed the largest reduction in rates of uninsurance among 3 income groups (< 100%, 100%-199%, and > or = 200% of the federal poverty level) between 1997 and 2003 (15.1%-8.7%). Significant reductions occurred in the proportion of children without a usual source of care in the target income group (9.4%-7.3%) and in the proportion of children without a provider visit in the past year (10.8%-9.8%). Other measures (unmet needs, delayed care, volume of provider visits, receipt of well-child care, and dental care) showed no significant changes over this time period. A separate multivariate analysis restricted to the State Children's Health Insurance Program target population in 2003 showed that children with continuous public coverage had significantly better access and utilization on all measures studied when compared with uninsured children and performed as well or better than children with continuous private coverage. CONCLUSIONS: Implementation of the State Children's Health Insurance Program is associated with substantial gains in public coverage for children in the target income group. Although some of these gains were offset by losses in private coverage, our findings demonstrate that public health insurance provides significant benefits in terms of access and utilization for children living in the target income group.

Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders.

Major depressive disorder (MDD) is a common, clinically heterogeneous disorder often found comorbid with other disorders. We studied recurrent, early-onset MDD (MDD-RE) and anxiety disorders in combination to define powerful phenotypes for genetic study. We used 87 large, extended Utah pedigrees to investigate linkage to 3 phenotypes: "MDD-RE;" "MDD-RE or anxiety;" and "MDD-RE and anxiety;" where in the latter definition the disorders must appear comorbid within an individual. Pedigrees ranged in size from 2 to 6 generations and contained 3 to 42 individuals affected with MDD or anxiety (718 total). In primary analyses, we identified three regions with at least suggestive genome-wide evidence for linkage on chromosomes 3centr, 7p, and 18q. Both 7p and 18q are replication findings for related phenotypes. The best linkage evidence was for a novel locus at 3p12.3-q12.3 (LOD = 3.88, "MDD-RE or anxiety") and 18q21.33-q22.2 (LOD = 3.75, "MDD-RE and anxiety"), a well-established susceptibility locus for bipolar disorder. In our secondary sex-specific analyses, we identified two further regions of interest on chromosomes 4q and 15q. Using linked pedigrees, we localized 3centr and 18q to 9.8 and 12.2 cM, respectively, with potential for further localization with the addition of markers in specific pedigrees. Our success in replication and novel locus identification illustrates the utility of large extended pedigrees for common disorders, such as MDD. Further, it supports the hypothesis that MDD and anxiety disorders have over-lapping genetic etiologies and suggests that comorbid diagnoses may be useful in defining more genetically homogeneous forms of MDD for linkage mapping.

Reducing health disparities among children.

The ultimate goal of providing public health insurance is to improve the health of low-income children. Yet, acknowledging the limitations of health insurance is important because children's health is shaped by a variety of factors, many of which cannot be influenced by increased access to health care. Health status is also affected by race, language, culture, geography, and socioeconomic class. This article summarizes current research about what health insurance can and cannot do in three areas: providing access to health care, reducing stress and worry for parents, and improving children's health status. This review reveals several important themes, including: A strong link between health insurance and access to care. Evidence that health insurance reduces parental stress--both financial and emotional. Mixed and inconclusive evidence about the link between health insurance and improved health status. The authors discuss some of the barriers to improving the health status of low-income children beyond increasing access to health care. They emphasize that ultimately, the underlying social inequities that lead to disparities in health status based on race, income, and education should be addressed.

The impact of borderline personality disorder on post-traumatic stress in the community: a study of health status, health utilization, and functioning.

This study examines impairment and health status and resource utilization among individuals with and without borderline personality disorder (BPD), all of whom had post-traumatic stress symptoms (PTSS). Using data from the community-based Piedmont Health Survey, 150 adult respondents who had experienced clinically significant PTSS during their life were identified. The Diagnostic Interview Schedule (DIS) Borderline Index was used to distinguish a subset of respondents who met criteria for BPD. Compared with adults with PTSS (n = 135), individuals with PTSS and BPD (PTSS-BPD) (n = 15) exhibited impaired health status and greater utilization of mental health services and psychotropic medications, as well as more functional impairment based on social, occupational, and early adverse life-event measures. Individuals with comorbid PTSS and BPD demonstrate greater overall impairment and usage of health care resources.

Predisposition locus for major depression at chromosome 12q22-12q23.2.

Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.