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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 2. |
- Handing, Elizabeth P., et al.
(författare)
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Heterogeneity in association between cognitive function and gait speed among older adults : an integrative data analysis study
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 6:4, s. 710-715
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing evidence shows that cognition and gait speed are associated and are important measures of health among older adults. However, previous studies have used different methods to assess these 2 outcomes and lack sufficient sample size to examine heterogeneity among subgroups. This study examined how the relationship between global cognitive function and gait speed are influenced by age, gender, and race utilizing an integrated data analysis approach.Method: Data on cognition (Montreal Cognitive Assessment [MoCA], Mini-Mental Status Examination [MMSE], and Modified Mini-Mental State Examination [3MSE]) and gait speed (range: 4–400 m) were acquired and harmonized from 25 research studies (n = 2802) of adults aged 50+ from the Wake Forest Older American Independence Center. Multilevel regression models examined the relationship between predicted values of global cognitive function (MoCA) and gait speed (4-m walk), including heterogeneity by age, race, and gender.Results: Global cognitive function and gait speed exhibited a consistent positive relationship among whites with increasing age, while this was less consistent for African Americans. That is, there was a low correlation between global cognitive function and gait speed among African Americans aged 50–59, a positive correlation in their 60s and 70s, then a negative correlation thereafter.Conclusion: Global cognition and gait speed exhibited a curvilinear U-shaped relationship among whites; however, the association becomes inverse in African Americans. More research is needed to understand this racial divergence and could aid in identifying interventions to maintain cognitive and gait abilities across subgroups.
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