Towards a long-term record of solar total and spectral irradiance

The variation of total solar irradiance (TSI) has been measured since 1978 and that of the spectral irradiance for an even shorter amount of time. Semi-empirical models are now available that reproduce over 80% of the measured irradiance variations. An extension of these models into the more distant past is needed in order to serve as input to climate simulations. Here we review our most recent efforts to model solar total and spectral irradiance on time scales from days to centuries and even longer. Solar spectral irradiance has been reconstructed since 1947. Reconstruction of solar total irradiance goes back to 1610 and suggests a value of about 1-1.5 Wm$^{-2}$ for the increase in the cycle-averaged TSI since the end of the Maunder minimum, which is significantly lower than previously assumed but agrees with other modern models. First steps have also been made towards reconstructions of solar total and spectral irradiance on time scales of millennia

Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE study

Red blood cell (RBC) traits provide insight into a wide range of physiological states and exhibit moderate to high heritability, making them excellent candidates for genetic studies to inform underlying biologic mechanisms. Previous RBC trait genome-wide association studies were performed primarily in European- or Asian-ancestry populations, missing opportunities to inform understanding of RBC genetic architecture in diverse populations and reduce intervals surrounding putative functional SNPs through fine-mapping. Here, we report the first fine-mapping of 6 correlated (Pearson's r range: |0.04-0.92|) RBC traits in up to 19 036 African Americans and 19 562 Hispanic/Latino participants of the Population Architecture using Genomics and Epidemiology consortium. Trans-ethnic meta-analysis of race/ethnic- and study-specific estimates for approximately 11 000 SNPs flanking 13 previously identified association signals as well as 150 000 additional array-wide SNPs was performed using inverse-variance meta-analysis after adjusting for study and clinical covariates. Approximately half of previously reported index SNP-RBC trait associations generalized to the trans-ethnic study population (p < 1.7 × 10 −4 ); previously unreported independent association signals within the ABO region reinforce the potential for multiple functional variants affecting the same locus. Trans-ethnic fine-mapping did not reveal additional signals at the HFE locus independent of the known functional variants. Finally, we identified a potential novel association in the Hispanic/Latino study population at the HECTD4/RPL6 locus for RBC count (p = 1.9 × 10 −7 ). The identification of a previously unknown association, generalization of a large proportion of known association signals, and refinement of known association signals all exemplify the benefits of genetic studies in diverse populations. © 2018 Wiley Periodicals, Inc

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10−8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10−8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy

On Computing Canonical Subsets of Graph-Based Behavioral Representations

Abstract. The collection of behavior protocols is a common practice in human factors research, but the analysis of these large data sets has always been a tedious and time-consuming process. We are interested in automatically finding canonical behaviors: a small subset of behavioral protocols that is most representative of the full data set, providing a view of the data with as few protocols as possible. Behavior protocols often have a natural graph-based representation, yet there has been little work applying graph theory to their study. In this paper we extend our recent algorithm by taking into account the graph topology induced by the paths taken through the space of possible behaviors. We applied this technique to find canonical web-browsing behaviors for computer users. By comparing identified canonical sets to a ground truth determined by expert human coders, we found that this graph-based metric outperforms our previous metric based on edit distance.