| 1. |
- Becker, Joel, et al.
(författare)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 2. |
- Dudding, Tom, et al.
(författare)
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Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.
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| 3. |
- Musharoff, Shaila, et al.
(författare)
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The inference of sex-biased human demography from whole-genome data
- 2019
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Sex-biased demographic events (“sex-bias”) involve unequal numbers of females and males. These events are typically inferred from the relative amount of X-chromosomal to autosomal genetic variation and have led to conflicting conclusions about human demographic history. Though population size changes alter the relative amount of X-chromosomal to autosomal genetic diversity even in the absence of sex-bias, this has generally not been accounted for in sex-bias estimators to date. Here, we present a novel method to identify sex-bias from genetic sequence data that models population size changes and estimates the female fraction of the effective population size during each time epoch. Compared to recent sex-bias inference methods, our approach can detect sex-bias that changes on a single population branch without requiring data from an outgroup or knowledge of divergence events. When applied to simulated data, conventional sex-bias estimators are biased by population size changes, especially recent growth or bottlenecks, while our estimator is unbiased. We next apply our method to high-coverage exome data from the 1000 Genomes Project and estimate a male bias in Yorubans (47% female) and Europeans (44%), possibly due to stronger background selection on the X chromosome than on the autosomes. Finally, we apply our method to the 1000 Genomes Project Phase 3 high-coverage Complete Genomics whole-genome data and estimate a female bias in Yorubans (63% female), Europeans (84%), Punjabis (82%), as well as Peruvians (56%), and a male bias in the Southern Han Chinese (45%). Our method additionally identifies a male-biased migration out of Africa based on data from Europeans (20% female). Our results demonstrate that modeling population size change is necessary to estimate sex-bias parameters accurately. Our approach gives insight into signatures of sex-bias in sexual species, and the demographic models it produces can serve as more accurate null models for tests of selection.
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| 4. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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