Intelligence is highly heritable
and a major determinant of human health and well-being
. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence
, but ...much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
We have integrated observations of tropospheric ozone, very short-lived (VSL) halocarbons and reactive iodine and bromine species from a wide variety of tropical data sources with the global CAM-Chem ...chemistry-climate model and offline radiative transfer calculations to compute the contribution of halogen chemistry to ozone loss and associated radiative impact in the tropical marine troposphere. The inclusion of tropospheric halogen chemistry in CAM-Chem leads to an annually averaged depletion of around 10% (~2.5 Dobson units) of the tropical tropospheric ozone column, with largest effects in the middle to upper troposphere. This depletion contributes approximately −0.10 W m−2 to the radiative flux at the tropical tropopause. This negative flux is of similar magnitude to the ~0.33 W m−2 contribution of tropospheric ozone to present-day radiative balance as recently estimated from satellite observations. We find that the implementation of oceanic halogen sources and chemistry in climate models is an important component of the natural background ozone budget and we suggest that it needs to be considered when estimating both preindustrial ozone baseline levels and long term changes in tropospheric ozone.
We report on work to increase the number of well-measured Type Ia supernovae (SNe Ia) at high redshifts. Light curves, including high signal-to-noise Hubble Space Telescope data, and spectra of six ...SNe Ia that were discovered during 2001, are presented. Additionally, for the two SNe with z > 1, we present ground-based J-band photometry from Gemini and the Very Large Telescope. These are among the most distant SNe Ia for which ground-based near-IR observations have been obtained. We add these six SNe Ia together with other data sets that have recently become available in the literature to the Union compilation. We have made a number of refinements to the Union analysis chain, the most important ones being the refitting of all light curves with the SALT2 fitter and an improved handling of systematic errors. We call this new compilation, consisting of 557 SNe, the Union2 compilation. The flat concordance ΛCDM model remains an excellent fit to the Union2 data with the best-fit constant equation-of-state parameter w = -0.997+0.050 -0.054(stat)+0.077 -0.082(stat + sys together) for a flat universe, or w = -1.038+0.056 -0.059(stat)+0.093 -0.097(stat + sys together) with curvature. We also present improved constraints on w(z). While no significant change in w with redshift is detected, there is still considerable room for evolution in w. The strength of the constraints depends strongly on redshift. In particular, at z >~ 1, the existence and nature of dark energy are only weakly constrained by the data. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with programs HST-GO-08585 and HST-GO-09075. Based, in part, on observations obtained at the ESO La Silla Paranal Observatory (ESO programs 67.A-0361 and 169.A-0382). Based, in part, on observations obtained at the Cerro-Tololo Inter-American Observatory (CTIO), National Optical Astronomy Observatory (NOAO). Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT). Based, in part, on observations obtained at the Gemini Observatory (Gemini programs GN-2001A-SV-19 and GN-2002A-Q-31). Based, in part on observations obtained at the Subaru Telescope. Based, in part, on data that were obtained at the W. M. Keck Observatory.
Single-nucleotide polymorphism was used in the construction of an expressed sequence tag map of Aegilops tauschii, the diploid source of the wheat D genome. Comparisons of the map with the rice and ...sorghum genome sequences revealed 50 inversions and translocations; 2, 8, and 40 were assigned respectively to the rice, sorghum, and Ae. tauschii lineages, showing greatly accelerated genome evolution in the large Triticeae genomes. The reduction of the basic chromosome number from 12 to 7 in the Triticeae has taken place by a process during which an entire chromosome is inserted by its telomeres into a break in the centromeric region of another chromosome. The original centromere-telomere polarity of the chromosome arms is maintained in the new chromosome. An intrachromosomal telomere-telomere fusion resulting in a pericentric translocation of a chromosome segment or an entire arm accompanied or preceded the chromosome insertion in some instances. Insertional dysploidy has been recorded in three grass subfamilies and appears to be the dominant mechanism of basic chromosome number reduction in grasses. A total of 64% and 66% of Ae. tauschii genes were syntenic with sorghum and rice genes, respectively. Synteny was reduced in the vicinity of the termini of modern Ae. tauschii chromosomes but not in the vicinity of the ancient termini embedded in the Ae. tauschii chromosomes, suggesting that the dependence of synteny erosion on gene location along the centromere-telomere axis either evolved recently in the Triticeae phylogenetic lineage or its evolution was recently accelerated.
Because of the huge size of the common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) genome of 17,300 Mb, sequencing and mapping of the expressed portion is a logical first step for gene ...discovery. Here we report mapping of 7104 expressed sequence tag (EST) unigenes by Southern hybridization into a chromosome bin map using a set of wheat aneuploids and deletion stocks. Each EST detected a mean of 4.8 restriction fragments and 2.8 loci. More loci were mapped in the B genome (5774) than in the A (5173) or D (5146) genomes. The EST density was significantly higher for the D genome than for the A or B. In general, EST density increased relative to the physical distance from the centromere. The majority of EST-dense regions are in the distal parts of chromosomes. Most of the agronomically important genes are located in EST-dense regions. The chromosome bin map of ESTs is a unique resource for SNP analysis, comparative mapping, structural and functional analysis, and polyploid evolution, as well as providing a framework for constructing a sequence-ready, BAC-contig map of the wheat genome.
Galaxies' rest-frame ultraviolet (UV) properties are often used to directly infer the degree to which dust obscuration affects the measurement of star formation rates (SFRs). While much recent work ...has focused on calibrating dust attenuation in galaxies selected at rest-frame ultraviolet wavelengths, locally and at high-z, here we investigate attenuation in dusty, star forming galaxies (DSFGs) selected at far-infrared wavelengths. By combining multiwavelength coverage across 0.15-500 mu min the COSMOS field, in particular making use of Herschel imaging, and a rich data set on local galaxies, we find an empirical variation in the relationship between the rest-frame UV slope ( beta ) and the ratio of infrared-to-ultraviolet emission (L sub(IR)/L sub(UV) = IRX) as a function of infrared luminosity, or total SFR. Both locally and at high-z, galaxies above SFR gap 50 M sub(middot in circle) yr super(-1) deviate from the nominal IRX- beta relation toward bluer colors by a factor proportional to their increasing IR luminosity. We also estimate contamination rates of DSFGs on high-z dropout searches of Lt1% at z lap 4-10, providing independent verification that contamination from very dusty foreground galaxies is low in Lyman-break galaxy searches. Overall, our results are consistent with the physical interpretation that DSFGs, e.g., galaxies with >50 M sub(middot in circle) yr super(-1), are dominated at all epochs by short-lived, extreme burst events, producing many young O and B stars that are primarily, yet not entirely, enshrouded in thick dust cocoons. The blue rest-frame UV slopes of DSFGs are inconsistent with the suggestion that most DSFGs at z ~ 2 exhibit steady-state star formation in secular disks.
On the basis of genomewide linkage studies of families affected with age-related maculopathy (ARM), we previously identified a significant linkage peak on 10q26, which has been independently ...replicated by several groups. We performed a focused SNP genotyping study of our families and an additional control cohort. We identified a strong association signal overlying three genes,
PLEKHA1, LOC387715, and
PRSS11. All nonsynonymous SNPs in this critical region were genotyped, yielding a highly significant association (
P < .00001) between
PLEKHA1/LOC387715 and ARM. Although it is difficult to determine statistically which of these two genes is most important, SNPs in
PLEKHA1 are more likely to account for the linkage signal in this region than are SNPs in
LOC387715; thus, this gene and its alleles are implicated as an important risk factor for ARM. We also found weaker evidence supporting the possible involvement of the
GRK5/RGS10 locus in ARM. These associations appear to be independent of the association of ARM with the Y402H allele of complement factor H, which has previously been reported as a major susceptibility factor for ARM. The combination of our analyses strongly implicates
PLEKHA1/LOC387715 as primarily responsible for the evidence of linkage of ARM to the 10q26 locus and as a major contributor to ARM susceptibility. The association of either a single or a double copy of the high-risk allele within the
PLEKHA1/LOC387715 locus accounts for an odds ratio of 5.0 (95% confidence interval 3.2–7.9) for ARM and a population attributable risk as high as 57%.
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a ...full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5
σ
, for all
δ
CP
values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3
σ
(5
σ
) after an exposure of 5 (10) years, for 50% of all
δ
CP
values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to
sin
2
2
θ
13
to current reactor experiments.
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT ...consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10
) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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