Parental origin of sequence variants associated with complex diseases

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldEffects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.info:eu-repo/grantAgreement/EC/FP7/21807

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

Broken home or drug using peers:"Significant relations"?

This study reports the results of a comparative survey with representative samples of 3,386 school attending youths, most of whom were 15 years of age and residing in five European cities. We found significant but low correlations between the type of family structure (intact family, model family, dual career houshold, single mother) and five forms of deviant behavior (tobacco smoking, cannabis use, delinquency, general drug use and a composite risk behavior scale). These correlations will be displaced by very high correlations with the level of drug using friends/peers. A number of differences were found between the youth from different cities in relation to these concerns. Results indicate differences among the cities in terms of the youths' relationships with drug use/deviance/risky behavior and family structure, gender role, and peer group behavior. This suggests that the cultural meanings associated with family, gender role, peer group, and risk behavior influence deviant outcomes

NOVEL INSERTION SEQUENCE-LIKE ELEMENT IS982 IN LACTOCOCCI

A novel insertion sequence-like (IS) element, designated IS982, was found on the lactose plasmid, pSK11L, from Lactococcus lactis subsp. cremoris SK11 and was located between the origin of replication and the oligopeptide transport gene cluster. The 1003-base pair (bp) IS982 was flanked by 18-bp perfect inverted repeats. IS982 contained an open reading frame encoding a putative transposase of 296 amino acids. An almost identical IS-like element (99% DNA sequence identity) was cloned and partially sequenced from the chromosome of Lactococcus lactis subsp. cremoris Wg2 with 17-bp perfect inverted repeats. Southern analysis indicated that in 12 lactococcal strains examined, IS982 was present with copy numbers ranging from 1 to at least 20. IS982 displayed sequence homology to the putative IS element RSBst-alpha from Bacillus stearothermophilus CU21. IS982 and RSBst-alpha were not related to other known insertion sequences and may represent a new family of IS elements. (C) 1995 Academic Press. Inc

International variations in youth drug use: the effect of individual behaviours, peer and family influences, and geographical location

This international study investigates factors underlying international variations in rates of youth drug use among representative samples of 15-year-olds in five cities (Bremen, n = 871; Dublin, n = 983; Groningen, n = 487; Newcastle upon Tyne, n = 880; Rome, n = 666). it reveals a higher level of drug use in English-speaking compared to continental populations, Drug use was associated with peer, family and individual factors. Logistic regression showed that family structure and sport were associated with lower rates and delinquent behaviour with higher rates of drug use in all cities and among males and females. Among males, city of residence also independently predicted drug use, The effect of traditional families and studiousness in reducing drug use was most evident for male drug use in low-use cities: higher rates of use in English-speaking cities appear partially due to the drug use of low-risk males. Copyright (C) 2000 S. Karger AG, Basel