Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

2016 United Kingdom national guideline on the sexual health care of men who have sex with men.

This guideline is intended for use in UK Genitourinary medicine clinics and sexual health services but is likely to be of relevance in all sexual health settings, including general practice and Contraception and Sexual Health (CASH) services, where men who have sex with men (MSM) seek sexual health care or where addressing the sexual health needs of MSM may have public health benefits. For the purposes of this document, MSM includes all gay, bisexual and all other males who have sex with other males and both cis and trans men. This document does not provide guidance on the treatment of particular conditions where this is covered in other British Association for Sexual Health and HIV (BASHH) Guidelines but outlines best practice in multiple aspects of the sexual health care of MSM. Where prevention of sexually transmitted infections including HIV can be addressed as an integral part of clinical care, this is consistent with the concept of combination prevention and is included. The document is designed primarily to provide guidance on the direct clinical care of MSM but also makes reference to the design and delivery of services with the aim of supporting clinicians and commissioners in providing effective services. Methodology This document was produced in accordance with the guidance set out in the BASHH CEG's document 'Framework for guideline development and assessment' published in 2010 at http://www.bashh.org/guidelines and with reference to the Agree II instrument. Following the production of the updated framework in April 2015, the GRADE system for assessing evidence was adopted and the draft recommendations were regraded. Search strategy (see also Appendix 1) Ovid Medline 1946 to December 2014, Medline daily update, Embase 1974 to December 2014, Pubmed NeLH Guidelines Database, Cochrane library from 2000 to December 2014. Search language English only. The search for Section 3 was conducted on PubMed to December 2014. Priority was given to peer-reviewed papers published in scientific journals, although for many issues evidence includes conference abstracts listed on the Embase database. In addition, for 'Identification of problematic recreational drug and alcohol use' section and 'Sexual problems and dysfunctions in MSM' section, searches included PsycINFO. Methods Article titles and abstracts were reviewed and if relevant the full text article was obtained. Priority was given to randomised controlled trial and systematic review evidence, and recommendations made and graded on the basis of best available evidence. Piloting and feedback The first draft of the guideline was circulated to the writing group and to a small group of relevant experts, third sector partners and patient representatives who were invited to comment on the whole document and specifically on particular sections. The revised draft was reviewed by the CEG and then reviewed by the BASHH patient/public panel and posted on the BASHH website for public consultation. The final draft was piloted before publication. Guideline update The guidelines will be reviewed and revised in five years' time, 2022

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Arachidonic acid enhances turnover of the dermal skeleton: Studies on zebrafish scales

Contains fulltext : 128133.pdf (publisher's version ) (Open Access