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Cited by 192Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsForensic and Genetic Research

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups

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Waters, Kevin M., Stram, Daniel O., Hassanein, Mohamed T., Le Marchand, Loïc, Wilkens, Lynne R., Maskarinec, Gertraud, Monroe, Kristine R., Kolonel, Laurence N., Altshuler, David, Henderson, Brian E., Haiman, Christopher A.·2010·PLoS Genetics
DOI 10.1371/journal.pgen.1001078PMC PMC2928808
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Abstract

It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10(-4)) and similar in all populations (odds ratios 1.09-1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; P(het) = 3.8×10(-4)). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding "synthetic associations" of rare mutations in T2D.

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Figure 1 Risk allele frequencies by racial/ethnic group. Risk allele frequencies for each variant in European Americans (Blue), African Americans (Yellow), Latinos (Purple), Japanese Americans (Red), and Native Hawaiians (Green). The order of the variants is based on the frequency of the risk allele in European Americans (high to low).
Figure 1 Risk allele frequencies by racial/ethnic group. Risk allele frequencies for each variant in European Americans (Blue), African Americans (Yellow), Latinos (Purple), Japanese Americans (Red), and Native Hawaiians (Green). The order of the variants is based on the frequency of the risk allele in European Americans (high to low).CC BY · PubMed Central
Figure 2 Predicted distribution of T2D risk from common variants by racial/ethnic group compared to European Americans. Comparison of the predicted risk distributions conveyed by the risk alleles relative to European Americans (Blue in Panels A–D): Panel A, African Americans (Red); Panel B, Latinos (Yellow); Panel C, Japanese Americans (Brown); Panel D, Native Hawaiians (Green). The x-axis is the log relative risk for each population centered (at log RR = 0) around the average total risk allele count in the multiethnic sample (18.5). The y-axis is the relative frequency of the population with that level of risk.
Figure 2 Predicted distribution of T2D risk from common variants by racial/ethnic group compared to European Americans. Comparison of the predicted risk distributions conveyed by the risk alleles relative to European Americans (Blue in Panels A–D): Panel A, African Americans (Red); Panel B, Latinos (Yellow); Panel C, Japanese Americans (Brown); Panel D, Native Hawaiians (Green). The x-axis is the log relative risk for each population centered (at log RR = 0) around the average total risk allele count in the multiethnic sample (18.5). The y-axis is the relative frequency of the population with that level of risk.CC BY · PubMed Central

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Metadata

Authors
Waters, K. M., Stram, D. O., Hassanein, M. T., Le Marchand, L., Wilkens, L. R., Maskarinec, G., Monroe, K. R., Kolonel, L. N., Altshuler, D., Henderson, B. E., & Haiman, C. A.
Affiliations
  • University of Southern California (US)
  • USC Norris Comprehensive Cancer Center (US)
  • University of Hawaiʻi at Mānoa (US)
  • Broad Institute (US)
Corresponding author
  • Waters, Kevin M.
  • Haiman, Christopher A.
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2010-08-26
Volume
6
Issue
8
Pages
e1001078
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1001078
PMC
PMC2928808
OpenAlex
W2145604455
Cited by
191
References
33
Citations by year
2026: 6 · 2025: 2 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 16 · 2015: 7 · 2014: 23 · 2013: 18 · 2012: 33
FWCI
13.30
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Human Genome Research Institute (U01HG004802)
  • National Cancer Institute (CA63464, U01CA063464, R37CA054281, R01CA054281, R01CA063464, CA 54281)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
type 2 diabetes, genetic risk variants, common genetic variants, European Americans, African Americans, Hispanic Americans, Japanese Americans, Native Hawaiians, ethnic differences in diabetes risk
MeSH terms
Adult, Aged, Alleles, Diabetes Mellitus, Type 2, Ethnicity, Europe, Female, Humans, Male, Middle Aged, Genetic Variation, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study

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