Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.
Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC3325177?pdf=render |
id |
doaj-7d17f3c0a15f4fcb806550a0a2cb0fcc |
---|---|
record_format |
Article |
spelling |
doaj-7d17f3c0a15f4fcb806550a0a2cb0fcc2020-11-25T02:12:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0184e100262110.1371/journal.pgen.1002621Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.Rong ChenErik CoronaMartin SikoraJoel T DudleyAlex A MorganAndres Moreno-EstradaGeoffrey B NilsenDavid RuauStephen E LincolnCarlos D BustamanteAtul J ButteMany disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed disparity in T2D incidence rates across ethnic populations.http://europepmc.org/articles/PMC3325177?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rong Chen Erik Corona Martin Sikora Joel T Dudley Alex A Morgan Andres Moreno-Estrada Geoffrey B Nilsen David Ruau Stephen E Lincoln Carlos D Bustamante Atul J Butte |
spellingShingle |
Rong Chen Erik Corona Martin Sikora Joel T Dudley Alex A Morgan Andres Moreno-Estrada Geoffrey B Nilsen David Ruau Stephen E Lincoln Carlos D Bustamante Atul J Butte Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. PLoS Genetics |
author_facet |
Rong Chen Erik Corona Martin Sikora Joel T Dudley Alex A Morgan Andres Moreno-Estrada Geoffrey B Nilsen David Ruau Stephen E Lincoln Carlos D Bustamante Atul J Butte |
author_sort |
Rong Chen |
title |
Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
title_short |
Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
title_full |
Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
title_fullStr |
Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
title_full_unstemmed |
Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
title_sort |
type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
description |
Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed disparity in T2D incidence rates across ethnic populations. |
url |
http://europepmc.org/articles/PMC3325177?pdf=render |
work_keys_str_mv |
AT rongchen type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT erikcorona type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT martinsikora type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT joeltdudley type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT alexamorgan type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT andresmorenoestrada type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT geoffreybnilsen type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT davidruau type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT stephenelincoln type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT carlosdbustamante type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases AT atuljbutte type2diabetesriskallelesdemonstrateextremedirectionaldifferentiationamonghumanpopulationscomparedtootherdiseases |
_version_ |
1724908305131765760 |