Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals

Background The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Results Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. Conclusions These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication

Measuring health-related quality of life for child maltreatment: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Child maltreatment causes substantial morbidity and mortality in the U.S. Morbidity associated with child maltreatment can reduce health-related quality of life. Accurately measuring the reduction in quality of life associated with child maltreatment is essential to the economic evaluation of educational programs and interventions to reduce the incidence of child maltreatment. The objective of this study was to review the literature for existing approaches and instruments for measuring quality-of-life for child maltreatment outcomes.</p> <p>Methods</p> <p>We reviewed the current literature to identify current approaches to valuing child maltreatment outcomes for economic evaluations. We also reviewed available preference-based generic QOL instruments (EQ-5D, HUI, QWB, SF-6D) for appropriateness in measuring change in quality of life due to child maltreatment.</p> <p>Results</p> <p>We did not identify any studies that directly evaluated quality-of-life in maltreated children. We identified 4 studies that evaluated quality of life for adult survivors of child maltreatment and 8 studies that measured quality-of-life for pediatric injury not related to child maltreatment. No study reported quality-of-life values for children younger than age 3.</p> <p>Currently available preference-based QOL instruments (EQ-5D, HUI, QWB, SF-6D) have been developed primarily for adults with the exception of the Health Utilities Index. These instruments do not include many of the domains identified as being important in capturing changes in quality of life for child maltreatment, such as potential for growth and development or psychological sequelae specific to maltreatment.</p> <p>Conclusion</p> <p>Recommendations for valuing preference-based quality-of-life for child maltreatment will vary by developmental level and type of maltreatment. In the short-term, available multi-attribute utility instruments should be considered in the context of the type of child maltreatment being measured. However, if relevant domains are not included in existing instruments or if valuing health for children less than 6 years of age, direct valuation with a proxy respondent is recommended. The choice of a proxy respondent is not clear in the case of child maltreatment since the parent may not be a suitable proxy. Adult survivors should be considered as appropriate proxies. Longer-term research should focus on identifying the key domains for measuring child health and the development of preference-based quality-of-life instruments that are appropriate for valuing child maltreatment outcomes.</p

Vertebrate Vitellogenin Gene Duplication in Relation to the “3R Hypothesis”: Correlation to the Pelagic Egg and the Oceanic Radiation of Teleosts

The spiny ray-finned teleost fishes (Acanthomorpha) are the most successful group of vertebrates in terms of species diversity. Their meteoric radiation and speciation in the oceans during the late Cretaceous and Eocene epoch is unprecedented in vertebrate history, occurring in one third of the time for similar diversity to appear in the birds and mammals. The success of marine teleosts is even more remarkable considering their long freshwater ancestry, since it implies solving major physiological challenges when freely broadcasting their eggs in the hyper-osmotic conditions of seawater. Most extant marine teleosts spawn highly hydrated pelagic eggs, due to differential proteolysis of vitellogenin (Vtg)-derived yolk proteins. The maturational degradation of Vtg involves depolymerization of mainly the lipovitellin heavy chain (LvH) of one form of Vtg to generate a large pool of free amino acids (FAA 150–200 mM). This organic osmolyte pool drives hydration of the ooctye while still protected within the maternal ovary. In the present contribution, we have used Bayesian analysis to examine the evolution of vertebrate Vtg genes in relation to the “3R hypothesis” of whole genome duplication (WGD) and the functional end points of LvH degradation during oocyte maturation. We find that teleost Vtgs have experienced a post-R3 lineage-specific gene duplication to form paralogous clusters that correlate to the pelagic and benthic character of the eggs. Neo-functionalization allowed one paralogue to be proteolyzed to FAA driving hydration of the maturing oocytes, which pre-adapts them to the marine environment and causes them to float. The timing of these events matches the appearance of the Acanthomorpha in the fossil record. We discuss the significance of these adaptations in relation to ancestral physiological features, and propose that the neo-functionalization of duplicated Vtg genes was a key event in the evolution and success of the teleosts in the oceanic environment

Pigmented villonodular synovitis of the thoracic spine: case report and review of the literature Sinovitis vellonodular pigmentada de la columna torácica: informe de un caso y revisión de la literatura Sinovitis pigmentada vilonodular da coluna torácica: relato de caso e revisão da literatura

Pigmented Villonodular Synovitis (PVNS), a lesion of the synovial tissues, is rarely found in the spine. We present a 73-year-old male with increasing lower extremity weakness and paresthesias. MRI scans revealed disc herniation and spinal cord compression at the T11-T12 and T12- L1 levels. Intraoperative exploration revealed an epidural mass originating in the T12 lamina, compressing the spinal cord at T11-T12. Pathologic examination was consistent with pigmented villonodular synovitis.<br>Sinovitis vellonodular pigmentada (PVNS) es una lesión del tejido sinovial y raramente se encuentra en la columna vertebral. Presentamos el caso de un hombre de 73 años de edad que mostró aumento de la flaqueza de la extremidad inferior y parestesias. El examen de imagen por resonancia magnética indicó una hernia de disco y compresión en el nivel de T11-T12 y T12-L1. La exploración quirúrgica evidenció una masa epidural originaria en T2 y compresión de la médula espinal a nivel de T11-T12. El examen patológico fue compatible con sinovitis vellonodular pigmentada.<br>Sinovitis pigmentada vilonodular (PVNS) é uma lesão do tecido sinovial e raramente é encontrada na coluna vertebral. Apresentamos o caso de um homem de 73 anos de idade com aumento de fraqueza da extremidade inferior e parestesia. O exame de imagem por ressonância magnética revelou hérnia de disco e compressão no nível T11-T12 e T12-L1. A exploração cirúrgica evidenciou massa epidural orginária em T2 e compressão da medula espinhal no nível de T11-T12. O exame patológico foi compatível com sinovitis pigmentada vilonodular

Transboundary Water Resources in Southern Africa: Conflict or cooperation?

Literature suggests a linkage between internationally shared water resources and conflict potential. Anthony R. Turton, Marian J. Patrick and Frédéric Julien examine transboundary water resource management in southern Africa, showing that empirical evidence indicates a propensity to cooperation. They use the Hydropolitical Complex concept to explain why states might choose cooperation over conflict where a critical shared resource could limit future development potential. Development (2006) 49, 22–31. doi:10.1057/palgrave.development.1100269

Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.

Background The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Results Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p &lt; 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p &lt; 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. Conclusions These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.</p