Dataset Information

Population-Matched Transcriptome Prediction Increases TWAS Discovery and Replication Rate.

ABSTRACT: Most genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS) focus on European populations; however, these results cannot always be accurately applied to non-European populations due to genetic architecture differences. Using GWAS summary statistics in the Population Architecture using Genomics and Epidemiology study, which comprises ∼50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we perform TWAS to determine gene-trait associations. We compared results using three transcriptome prediction models derived from Multi-Ethnic Study of Atherosclerosis populations: the African American and Hispanic/Latino (AFHI) model, the European (EUR) model, and the African American, Hispanic/Latino, and European (ALL) model. We identified 240 unique significant trait-associated genes. We found more significant, colocalized genes that replicate in larger cohorts when applying the AFHI model than the EUR or ALL model. Thus, TWAS with population-matched transcriptome models have more power for discovery and replication, demonstrating the need for more transcriptome studies in diverse populations.

SUBMITTER: Geoffroy E

PROVIDER: S-EPMC7721644 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Population-Matched Transcriptome Prediction Increases TWAS Discovery and Replication Rate.

Geoffroy Elyse E Gregga Isabelle I Wheeler Heather E HE

iScience 20201123 12

Most genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS) focus on European populations; however, these results cannot always be accurately applied to non-European populations due to genetic architecture differences. Using GWAS summary statistics in the Population Architecture using Genomics and Epidemiology study, which comprises ∼50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we perform TWAS to determine gene-trai ...[more]

PMID: 33313492

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Project description:Most woodland caribou (Rangifer tarandus caribou) populations are declining primarily because of unsustainable predation resulting from habitat-mediated apparent competition. Wolf (Canis lupus) reduction is an effective recovery option because it addresses the direct effect of predation. We considered the possibility that the indirect effects of predation might also affect caribou population dynamics by adversely affecting summer foraging behaviour. If spring and/or summer nutrition was inadequate, then supplemental feeding in fall might compensate for that limitation and contribute to population growth. Improved nutrition and therefore body condition going into winter could increase adult survival and lead to improved reproductive success the next spring. To test that hypothesis, we fed high-quality food pellets to free-ranging caribou in the Kennedy Siding caribou herd each fall for six years, starting in 2014, to see if population growth rate increased. Beginning in winter 2015-16, the Province of British Columbia began a concurrent annual program to promote caribou population increase by attempting to remove most wolves within the Kennedy Siding and the adjacent caribou herds' ranges. To evaluate the impact of feeding, we compared lambdas before and after feeding began, and to the population trend in the adjacent Quintette herd over the subsequent four years. Supplemental feeding appeared to have an incremental effect on population growth. Population growth of the Kennedy Siding herd was higher in the year after feeding began (λ = 1.06) compared to previous years (λ = 0.91) and to the untreated Quintette herd (λ = 0.95). Average annual growth rate of the Kennedy Siding herd over the subsequent four years, where both feeding and wolf reduction occurred concurrently, was higher than in the Quintette herd where the only management action in those years was wolf reduction (λ = 1.16 vs. λ = 1.08). The higher growth rate of the Kennedy Siding herd was due to higher female survival (96.2%/yr vs. 88.9%/yr). Many caribou were in relatively poor condition in the fall. Consumption of supplemental food probably improved their nutritional status which ultimately led to population growth. Further feeding experiments on other caribou herds using an adaptive management approach would verify the effect of feeding as a population recovery tool. Our results support the recommendation that multiple management actions should be implemented to improve recovery prospects for caribou.

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Population-Matched Transcriptome Prediction Increases TWAS Discovery and Replication Rate.

Publications

Population-Matched Transcriptome Prediction Increases TWAS Discovery and Replication Rate.

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