Mixed Race Studies

Skin pigmentation, biogeographical ancestry and admixture mapping

Human Genetics
Volume 112, Issue 4 (April 2003)
pages 387-399

Mark D. Shriver, Professor of Anthropology
Pennsylvania State University

Esteban J. Parra
Department of Anthropology
University of Toronto at Mississauga

Sonia Dios
Department of Anthropology
Pennsylvania State University

Carolina Bonilla
Department of Anthropology
Pennsylvania State University

Heather Norton
Department of Anthropology
Pennsylvania State University

Celina Jovel
Department of Anthropology
Pennsylvania State University

Carrie Pfaff
Department of Anthropology
Pennsylvania State University

Cecily Jones
National Human Genome Center
Howard University, Washington, D.C.

Aisha Massac
National Human Genome Center
Howard University, Washington, D.C.

Neil Cameron
Takeway Media, London

Archie Baron
Takeway Media, London

Tabitha Jackson
Takeway Media, London

George Argyropoulos
Pennington Center for Biomedical Research, Baton Rouge, Louisiana

Li Jin
Department of Environmental Health
University of Cincinnati, Cincinnati, Ohio

Clive J. Hoggart
Department of Epidemiology and Population Health
London School of Hygiene and Tropical Medicine

Paul M. McKeigue
Department of Epidemiology and Population Health
London School of Hygiene and Tropical Medicine

Rick A. Kittles
National Human Genome Center
Howard University, Washington, D.C.

Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R²=0.21, P<0.0001 for the African-American sample and R²=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and applications of ancestry estimates in biomedical research are discussed.

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Race as a Social Construct in Head and Neck Cancer Outcomes

Otolaryngology—Head Neck Surgery
Volume 144, Number 3 (March 2011)
pages 381-389
DOI: 10.1177/0194599810393884

Maria J. Worsham, PhD
Department of Otolaryngology/Head and Neck Surgery
Henry Ford Health System, Detroit, Michigan

George Divine, PhD
Biostatistics and Research Epidemiology
Henry Ford Health System, Detroit, Michigan

Rick A. Kittles, PhD
Section of Hematology/Oncology, Department of Medicine and Division of Epidemiology and Biostatistics
School of Public Health, University of Illinois, Chicago

Objective. The authors examined ancestry informative markers (AIMs) to estimate the amount of population admixture and control for this heterogeneity for stage and survival in a primary head and neck squamous cell carcinoma (HNSCC) cohort.

Study Design. Historical cohort study.

Setting. Integrated health care system.

Subjects. The cohort comprised 358 patients with HNSCC who self-reported race as Caucasian American (CA), African American (AA), or other.

Methods. DNA was interrogated for West African (WA) and European genetic background by genotyping AIMs. Associations of race (self-report or WA ancestry) with stage and survival were analyzed using logistic regression and Cox regression modeling. A subgroup analysis for diagnosis (late vs early stage) and survival (time to death) and WA ancestry was performed for self-reported AAs.

Results. There were significant associations between stage and self-reported race (P = .04 [univariate]) and with cancer site (oropharynx: P = .014; hypopharynx: P = .026 [multivariate]). For prognosis, there were significant multivariate associations between stage (P = .002), age (>65 years, P < .001), and cancer site (hypopharynx: P < .001; oral cavity: P = .049), but self-reported race was not associated with overall survival. Interestingly, there was no association with degree of WA ancestry and stage or survival. In the subgroup analysis of genetic ancestry among self-reported AAs, cancer site remained an independent risk factor for stage (other site: P = .026) and survival (oropharynx: P = .036). Late stage persisted as an independent variable for poor survival (P = .032).

Conclusions. Stratification within AAs by WA ancestry revealed no correlation with stage or survival, suggesting that HNSCC outcomes with race may be owing to social/behavior factors rather than biological differences.

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