Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λ(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies

Pregnancy related back pain, is it related to aerobic fitness? A longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Low back pain with onset during pregnancy is common and approximately one out of three women have disabling pain. The pathogenesis of the pain condition is uncertain and there is no information on the role of physical fitness. Whether poorer physical conditioning is a cause or effect of back pain is also disputed and information from prospective studies needed.</p> <p>Methods</p> <p>A cohort of pregnant women, recruited from maternal health care centers in central Sweden, were examined regarding estimated peak oxygen uptake by cycle ergometer test in early pregnancy, reported physical activity prior to pregnancy, basic characteristics, back pain during pregnancy and back pain postpartum.</p> <p>Results</p> <p>Back pain during the current pregnancy was reported by nearly 80% of the women. At the postpartum appointment this prevalence was 40%. No association was displayed between estimated peak oxygen uptake and incidence of back pain during and after pregnancy, adjusted for physical activity, back pain before present pregnancy, previous deliveries, age and weight. A significant inverse association was found between estimated peak oxygen uptake and back pain intensity during pregnancy and a direct association post partum, in a fully adjusted multiple linear regression analysis.</p> <p>Conclusions</p> <p>Estimated peak oxygen uptake and reported physical activity in early pregnancy displayed no influence on the onset of subsequent back pain during or after pregnancy, where the time sequence support the hypothesis that poorer physical deconditioning is not a cause but a consequence of the back pain condition. The mechanism for the attenuating effect of increased oxygen uptake on back pain intensity is uncertain.</p

Multifaceted value profiles of forest owner categories in South Sweden: The river helge å catchment as a case study

Forest landscapes provide benefits from a wide range of goods, function and intangible values. But what are different forest owner categories\u27 profiles of economic use and non-use values? This study focuses on the complex forest ownership pattern of the River Helge å catchment including the Kristianstad Vattenrike Biosphere Reserve in southern Sweden. We made 89 telephone interviews with informants representing the four main forest owner categories. Our mapping included consumptive and non-consumptive direct use values, indirect use values, and non-use values such as natural and cultural heritage. While the value profiles of non-industrial forest land owners and municipalities included all value categories, the forest companies focused on wood production, and the Swedish Environmental Protection Agency on nature protection. We discuss the challenges of communicating different forest owners\u27 economic value profiles among stakeholders, the need for a broader suite of forest management systems, and fora for collaborative planning. © 2013 The Author(s)

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis