2017 William Allan Award Introduction : Kari Stefansson

Peer reviewe

Stochastic Rainfall-runoff Model with Explicit Soil Moisture Dynamics

Stream runoff is perhaps the most poorly represented process in ecohydrological stochastic soil moisture models. Here we present a rainfall-runoff model with a new stochastic description of runoff linked to soil moisture dynamics. We describe the rainfall-runoff system as the joint probability density function (PDF) of rainfall, soil moisture and runoff forced by random, instantaneous jumps of rainfall. We develop a master equation for the soil moisture PDF that accounts explicitly for a general state-dependent rainfall-runoff transformation. This framework is then used to derive the joint rainfall-runoff and soil moisture-runoff PDFs. Runoff is initiated by a soil moisture threshold and a linear progressive partitioning of rainfall based on the soil moisture status. We explore the dependence of the PDFs on the rainfall occurrence PDF (homogeneous or state-dependent Poisson process) and the rainfall magnitude PDF (exponential or mixed-exponential distribution). We calibrate the model to 63 years of rainfall and runoff data from the Upper Little Tennessee watershed (USA) and show how the new model can reproduce the measured runoff PDF

Estimation of the Multiple Testing Burden for Genomewide Association Studies of Common Variants

Genomewide association studies are an exciting strategy in genetics, recently becoming feasible. While pioneering studies are being underway, it is already clear that the analytic issue of determining the significance of results presents a challenge to the wide community of researchers. Rather than each study engaging in independent evaluation, there is need in the community to have standards set for whole-genome significance. 
We have therefore undertaken the task of developing such standards, based on data collected with collaborators in the International Haplotype Map Consortium. We report an estimated burden of a million independent tests genomewide in Europeans, and twice that number in Africans. We further identify the sensitivity of the testing burden to the required significance level, with implications to staged design of association studies.
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A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness.

Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10-25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10-8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine

Young stars and non-stellar emission in the aligned radio galaxy 3C 256

We present ground-based images of the z=1.824 radio galaxy 3C 256 in the standard BVRIJHK filters and an interference filter centered at 8800A, a Hubble Space Telescope image in a filter dominated by Ly-alpha emission (F336W), and spectra covering rest-frame wavelengths from Ly-alpha to [O III] 5007. Together with published polarimetry observations, we use these to decompose the overall spectral energy distribution into nebular continuum emission, scattered quasar light, and stellar emission. The nebular continuum and scattered light together comprise half (one third) of the V-band (K-band) light within a 4-arcsec aperture, and are responsible for the strong alignment between the optical/near-infrared light and the radio emission. The stellar emission is dominated by a population estimated to be 100-200 Myr old (assuming a Salpeter IMF), and formed in a short burst with a peak star formation rate of 1-4x10^3 Msun/yr. The total stellar mass is estimated to be no more than 2x10^{11} Msun, which is far less than other luminous radio galaxies at similar redshifts, and suggests that 3C 256 will undergo further star formation or mergers.Comment: 35 pages including 10 figures; to appear in Nov 10 Ap

Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology

Genome-wide association studies have uncovered hundreds of DNA changes associated with complex disease. The ultimate promise of these studies is the understanding of disease biology; this goal, however, is not easily achieved because each disease has yielded numerous associations, each one pointing to a region of the genome, rather than a specific causal mutation. Presumably, the causal variants affect components of common molecular processes, and a first step in understanding the disease biology perturbed in patients is to identify connections among regions associated to disease. Since it has been reported in numerous Mendelian diseases that protein products of causal genes tend to physically bind each other, we chose to approach this problem using known protein–protein interactions to test whether any of the products of genes in five complex trait-associated loci bind each other. We applied several permutation methods and find robustly significant connectivity within four of the traits. In Crohn's disease and rheumatoid arthritis, we are able to show that these genes are co-expressed and that other proteins emerging in the network are enriched for association to disease. These findings suggest that, for the complex traits studied here, associated loci contain variants that affect common molecular processes, rather than distinct mechanisms specific to each association.Massachusetts Institute of Technology (MIT IDEA2 Program)Harvard University. Biological and Biomedical Sciences ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (NICHD RO1 grant HD055150-03)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (K08 NIH-NIAMS career development award (AR055688))National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DK083756)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DK086502)Denmark. Forskningsradet for Sundhed og SygdomCenter for the Study of Inflammatory Bowel Diseas