Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations

Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations

Bibliographic Details
Main Author: Zhang, Ju
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2021
Subjects:
Bioinformatics
Biostatistics
Epidemiology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1619455882746982
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case16194558827469822021-08-03T07:17:18Z Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations Zhang, Ju Bioinformatics Biostatistics Epidemiology As the number of genome-wide association studies conducted in both single- and multi-ancestral populations increase, the significance of estimating genetic correlation for complex traits has become more enormous. Brown et al. expanded the definition of genetic correlation to trans-ancestral context and developed the method Popcorn to estimate genetic correlation using summary statistics. Although Popcorn produces unbiased estimators of genetic correlation and heritability, it requires large sample sizes, large number of SNPs and matched external reference panels, thus limiting its utility to homogenous populations. We performed evaluation and extension on the method of Popcorn. First, we evaluated Popcorn under several parameters and circumstances: sample size, number of SNPs, sample size of external reference panel, various population pairs, inappropriate external reference panel and admixed population involved. We found the minimum sample size of external reference panel, summary statistics and number of SNPs required to accurately estimate both the genetic correlation and heritability with a lower (0.1), middle (0.5) and larger value (0.9). Moreover, the number of individuals and SNPs needed to produce accurate and stable estimates was directly proportional with heritability in Popcorn. Although the true value of genetic correlation was not related to the minimum number of sample size, Popcorn needed an increasing number of SNPs for higher genetic correlation to provide accurate estimates. Furthermore, misrepresentation of the reference panel overestimated the genetic correlation by 20% and heritability by 60%. Second, we extended this method to accurately estimate genetic correlation and heritability in admixed populations by updating LD scores using PC-adjusted genotypes to eliminate the effect of long-range LD induced by admixed populations. Lastly, we evaluate the method by varying the number of individuals in the external reference panel, summary statistic sample size, number of SNPs, number of PCs, and the proportion of causal variants using simulation studies. The evaluation provides plenty information for researchers applying Popcorn and extended method to obtain reliable and confidence results of estimation of both genetic correlation and heritability as reference. The method is implemented in a Python package named cov-Popcorn. 2021-06-21 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1619455882746982 http://rave.ohiolink.edu/etdc/view?acc_num=case1619455882746982 restricted--full text unavailable until 2023-05-30 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Bioinformatics
Biostatistics
Epidemiology
spellingShingle Bioinformatics
Biostatistics
Epidemiology
Zhang, Ju
Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
author Zhang, Ju
author_facet Zhang, Ju
author_sort Zhang, Ju
title Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
title_short Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
title_full Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
title_fullStr Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
title_full_unstemmed Trans-Ancestral Genetic Correlation Estimates from Summary Statistics for Admixed Populations
title_sort trans-ancestral genetic correlation estimates from summary statistics for admixed populations
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2021
url http://rave.ohiolink.edu/etdc/view?acc_num=case1619455882746982
work_keys_str_mv AT zhangju transancestralgeneticcorrelationestimatesfromsummarystatisticsforadmixedpopulations
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