Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Study and Characterization of a Two-Way Satellite Time and Frequency Transfer Link using Software-Defined Radio solutions to both code and carrier-phase signals

International audienceThis paper presents a complete study and characterization of a two-way satellite time and frequency transfer link between two remote earth stations equipped with analog modems and software-defined radio receivers driven by atomic clocks. Techniques based on code-phase and carrier-phase measurements were developed to compute time and frequency deviations between these clocks. A comparison of different methods using conventional bandwidth, broadband, carrier-phase information and software-defined radio solution is given. In addition, the paper is completed by a description of calibration aspects, more specifically on the software-defined radio link, an essential step in calculating the differences between remote time scales with very high accuracy, reaching a level of uncertainty of the order of 0.5 nanosecond

Evaluation of BDS Time Transfer on Multiple Baselines for UTC

International audienc

Evaluation of BDS Time Transfer on Multiple Baselines for UTC

International audienc

The ICRF-3: Proposed Roadmap to the Next Generation International Celestial Reference Frame

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision, spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2000 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K- band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

ICRF-3: Roadmap to the next generation ICRF

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision as well as the spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2200 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K-band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern hemisphere precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

The ICRF-3: Proposed Roadmap to the Next Generation International Celestial Reference Frame

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision, spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2000 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K- band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

Final report of key comparison CCM.G-K1: International comparison of absolute gravimeters ICAG2009

International audienc