Self-reported ethnicity, genetic structure and the impact of population stratification in a multiethnic study
Open accessAbstract
It is well-known that population substructure may lead to confounding in case-control association studies. Here, we examined genetic structure in a large racially and ethnically diverse sample consisting of five ethnic groups of the Multiethnic Cohort study (African Americans, Japanese Americans, Latinos, European Americans and Native Hawaiians) using 2,509 SNPs distributed across the genome. Principal component analysis on 6,213 study participants, 18 Native Americans and 11 HapMap III populations revealed four important principal components (PCs): the first two separated Asians, Europeans and Africans, and the third and fourth corresponded to Native American and Native Hawaiian (Polynesian) ancestry, respectively. Individual ethnic composition derived from self-reported parental information matched well to genetic ancestry for Japanese and European Americans. STRUCTURE-estimated individual ancestral proportions for African Americans and Latinos are consistent with previous reports. We quantified the East Asian (mean 27%), European (mean 27%) and Polynesian (mean 46%) ancestral proportions for the first time, to our knowledge, for Native Hawaiians. Simulations based on realistic settings of case-control studies nested in the Multiethnic Cohort found that the effect of population stratification was modest and readily corrected by adjusting for race/ethnicity or by adjusting for top PCs derived from all SNPs or from ancestry informative markers; the power of these approaches was similar when averaged across causal variants simulated based on allele frequencies of the 2,509 genotyped markers. The bias may be large in case-only analysis of gene by gene interactions but it can be corrected by top PCs derived from all SNPs.
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Wang et al. estimated 74% Hawaiian ancestry based on 300 AIMs in Multiethnic Cohort subjects reporting Native Hawaiian heritage.
“Overall, our results are roughly comparable to the report by Wang et al. [53] that estimated 74% Hawaiian ancestry based on 300 AIMs that were tested in Multiethnic Cohort subjects, who reported Native Hawaiian heritage.”
From Population Genetic Structure and Origins of Native Hawaiians in the Multiethnic Cohort Study (2012) · cites this paper as [53]
The Results (AIMs and individual admixture) report 74% average Hawaiian ancestry for MEC participants who reported two Hawaiian-only parents, not for all participants reporting Native Hawaiian heritage. The Methods (Ancestry Informative Markers and individual admixture) say the ancestry estimates used 400 P3-HAW AIMs; the 300-AIM panel was assessed for distinguishing populations, not for producing the 74% estimate. (LLM, conf=0.92)
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- Authors
- Wang, H., Haiman, C. A., Kolonel, L. N., Henderson, B. E., Wilkens, L. R., Le Marchand, L., & Stram, D. O.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- University of Southern California (US)
- Corresponding author
- Wang, Hansong
- Venue
- Human Genetics
- Published
- 2010-05-25
- Volume
- 128
- Issue
- 2
- Pages
- 165-177
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- PMC
- PMC3057055
- OpenAlex
- W2054618048
- Cited by
- 45
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 4 · 2013: 4 · 2012: 7
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ministerio de Economía y Competitividad
- National Institutes of Health
- National Cancer Institute (R37 CA 54281, P01CA 33619, R37CA054281, R01CA63464, R01CA063464, U01 CA98758, U01CA098758, P01CA033619)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
- Keywords
- population stratification, genetic ancestry, self-reported ethnicity, Multiethnic Cohort Study, Native Hawaiians, Polynesian ancestry, ancestry informative markers, case-control association, confounding, principal component analysis, gene-gene interaction, HapMap populations
- MeSH terms
- Asian, Black or African American, Data Collection, Ethnicity, Gene Frequency, Genotype, Hispanic or Latino, Humans, Male, Cohort Studies, Case-Control Studies, Polymorphism, Single Nucleotide, Genetic Structures, Population Groups, Black People, White People, Asian People, Native Hawaiian or Pacific Islander, Native Hawaiian or Other Pacific Islander
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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