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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.
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).
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.
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.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
This chapter discusses the development of the adult population of Leydig cells from the stem cell precursor through the progenitor and immature Leydig cell stages. The morphogenetic events of early testis differentiation are controlled by the Sry (sex-determining region on the Y chromosome) gene. Lack of luteinizing hormone (LH) stimulation results in reduced steroidogenic enzyme activities and in Leydig cell atrophy. As men age, progressive decreases in serum concentrations of testosterone occur. Associated with these decreases are significant health consequences, including reduced sexual function, energy, muscle function, and bone density, and increased frailty and cognitive impairment. A number of hypotheses have been put forward over the years to explain changes that occur in aging cells, including late-onset gene expression, telomere shortening, gene modifications, changes in the immune system, and accumulated reactive oxygen-induced damage to DNA, lipids, and/or proteins.