| 1. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 2. |
- Eastwood, Michael W., et al.
(författare)
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The Radio Sky at Meter Wavelengths: M-mode Analysis Imaging with the OVRO-LWA
- 2018
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 156:1
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Tidskriftsartikel (refereegranskat)abstract
- A host of new low-frequency radio telescopes seek to measure the 21 cm transition of neutral hydrogen from the early universe. These telescopes have the potential to directly probe star and galaxy formation at redshifts 20 ≳ z ≳ 7 but are limited by the dynamic range they can achieve against foreground sources of low-frequency radio emission. Consequently, there is a growing demand for modern, high-fidelity maps of the sky at frequencies below 200 MHz for use in foreground modeling and removal. We describe a new wide-field imaging technique for drift-scanning interferometers: Tikhonov-regularized m-mode analysis imaging. This technique constructs images of the entire sky in a single synthesis imaging step with exact treatment of wide-field effects. We describe how the CLEAN algorithm can be adapted to deconvolve maps generated by m-mode analysis imaging. We demonstrate Tikhonov-regularized m-mode analysis imaging using the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA) by generating eight new maps of the sky north of δ = -30° with 15′ angular resolution at frequencies evenly spaced between 36.528 and 73.152 MHz and ∼800 mJy beam-1thermal noise. These maps are a 10-fold improvement in angular resolution over existing full-sky maps at comparable frequencies, which have angular resolutions ≥2°. Each map is constructed exclusively from interferometric observations and does not represent the globally averaged sky brightness. Future improvements will incorporate total power radiometry, improved thermal noise, and improved angular resolution due to the planned expansion of the OVRO-LWA to 2.6 km baselines. These maps serve as a first step on the path to the use of more sophisticated foreground filters in 21 cm cosmology incorporating the measured angular and frequency structure of all foreground contaminants.
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| 3. |
- Anderson, Marin M., et al.
(författare)
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Simultaneous Search for Prompt Radio Emission Associated with the Short GRB 170112A Using the All-sky Imaging Capability of the OVRO-LWA
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 864:1
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Tidskriftsartikel (refereegranskat)abstract
- We have conducted the most sensitive low-frequency (below 100 MHz) search to date for prompt, low-frequency radio emission associated with short-duration gamma-ray bursts (GRBs), using the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA). The OVRO-LWA's nearly full-hemisphere field of view (similar to 20,000 square degrees) allows us to search for low-frequency (sub-100 MHz) counterparts for a large sample of the subset of GRB events for which prompt radio emission has been predicted. Following the detection of short GRB 170112A by Swift, we used all-sky OVRO-LWA images spanning one hour prior to and two hours following the GRB event to search for a transient source coincident with the position of GRB 170112A. We detect no transient source to within a 3 sigma flux density limit of 4.5. Jy at 13 s timescales for frequencies spanning 27-84. MHz. We place constraints on a number of models predicting prompt, low-frequency radio emission accompanying short GRBs and their potential binary neutron star merger progenitors, and place an upper limit of L-radio/L gamma less than or similar to 3.5 x 10(-6) on the fraction of energy released in the prompt radio emission, under the assumptions of negligible scattering of the radio pulse and beaming of emission along the line of sight. These observations serve as a pilot effort for a program targeting a wider sample of both short and long GRBs with the OVRO-LWA, including bursts with confirmed redshift measurements that are critical to placing constraining limits on prompt radio emission models, as well as a program for the follow-up of gravitational wave compact binary coalescence events detected by advanced LIGO and Virgo.
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| 4. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 5. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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