Research orientation
I am an anthropological geneticist with a primary research focus on the genetic and environmental factors influencing type 2 diabetes risk in American Indians, a population disproportionately affected by this disorder. I investigate these factors using data from families and statistical genetics methods. In my secondary research, I use paleopathology and skeletal biology to examine the use and treatment of domesticated dogs in prehistory. These disparate research areas are connected by my interest in understanding the relationship between biological variation, cultural practices, and the environment.
My anthropological genetics research is broadly focused on the genetic and environmental factors contributing to complex phenotypes (traits) in living humans. Variation in complex phenotypes is influenced by the combined effects of multiple genetic and environmental factors and their interactions. "Environment" in this context includes age, sex, and lifestyle variables such as diet or smoking. Most phenotypes are complex, including susceptibility to many diseases of public health importance, for example, cardiovascular disease, diabetes, cancer, and addiction. Identification of complex disease risk factors is essential to understanding biologic pathways and for developing treatments and interventions. Both quantitative (continuous) and qualitative (discrete) phenotypes can be complex. An individual genetic factor may have only a small effect on the variation of a complex phenotype, making it very difficult to detect. This contrasts with the case of simpler "Mendelian" phenotypes that are influenced by a major gene with a large effect size. The identification of the genetic and environmental factors influencing a complex phenotype is further complicated by individual and population variation in the combinations of factors that influence the phenotype and in the relative effect sizes of the factors. In my research, I use specialized statistical genetics methods to identify and characterize the genetic and environmental components of complex phenotypes. These include linkage analyses, which can be used to map variation in phenotypes to chromosomal regions represented by genetic markers, and tests for association between phenotype variation and single nucleotide polymorphisms (SNPs) within genes. Many statistical genetics methods require or can accommodate data from families. Genotypes, phenotype assays, and other wet lab products are integral to my research. However, wet lab-based research explicitly is not a component of my current position in the Department of Anthropology at the University of Oklahoma.
Skeletal biology research
I use skeletal biology and paleopathology to investigate the use and treatment of dogs by Native Americans in prehistory. Dogs were the only domesticated mammal kept by Native North Americans prior to European contact. Deliberate dog burial, both within and outside of human graves, was common in the Midwest, Midsouth and Southeast during the Archaic period (8000-3000 BP). Typically, Archaic peoples in these regions were highly mobile hunter-gatherers. A post-Archaic decline in the number of dog burials may reflect changes in the functional and/or cultural roles of dogs in Native American societies as sedentism increased and food production intensified. Although there has been considerable speculation about dog use in prehistory, much of our current understanding is based on ethnographic analogy rather than on direct evidence.
In my dissertation research, I used data from 455 dogs from Archaic through early historic period archaeological sites in Alabama, Kentucky, Tennessee, and Illinois to investigate geographic, temporal, and other variation in dog health, size, and population age and sex structure. I found that older age, but not sex, size, or life experience as indicated by a variety of skeletal and dental pathologies, was a significant factor in a dog's selection for burial in human graves at Late Archaic sites. Significantly more males than expected occurred at Archaic and at post-Archaic sites, potentially due to differential burial by sex or to a preponderance of males in the living population. More males would occur where population size was managed by culling females, or where preferences for males led to increased care of dogs of that sex. Dog size did not change significantly over time. I found patterns of variation in dental pathology consistent with local and temporal differences in dog diet and activity. High frequencies of vertebral, rib, and skull fractures in all time periods are consistent with abuse by humans and/or aggressive encounters with other animals, including through dog fighting or the use of dogs in hunting. The dogs exhibited multiple pathologies consistent with use as beasts of burden; the data suggest this use of dogs decreased over time.
Previous genetics research
My previous genetics research focused on the genetic and environmental components of quantitative variation in hemostasis (blood clotting) phenotypes. Data were from families participating in the San Antonio Family Heart Study (SAFHS), an investigation of cardiovascular disease in low-income Hispanic families. Cardiovascular disease is the leading cause of death in this population. The hemostasis phenotypes are risk factors for cardiovascular diseases.
Using a variance components-based approach and after accounting for measured covariates including age, sex, medications, and lifestyle factors, I found that genetic factors contributed significantly to variation in each of the hemostasis phenotypes, with additive genetic effects explaining between 20 and 60 percent phenotypic variation. Significant genetic correlations occurred between type 2 diabetes and several hemostasis phenotypes, suggesting that the same genes that influence cardiovascular disease risk pleiotropically contribute to type 2 diabetes risk. In a related project, I used genome-wide linkage scans to identify a significant quantitative trait locus (QTL) for thrombin-activatable fibrinolysis inhibitor (TAFI) on chromosome 13q.
In addition to my research on complex disease risk, I investigated the genetic components of normal variation in hand, foot and eye preference, using data from the San Antonio Family Diabetes/Gallbladder Study. There has been considerable interest among anthropologists and others in the evolution of laterality, but the factors contributing to side preference are poorly understood. I found a weak but significant heritability for self-reported handedness and other side preferences, indicating that genes are an important component of laterality. Genome-wide linkage scans revealed QTLs for hand preference and eye preference on chromosomes 12q and 22pter, respectively.
Current genetics research and research goals
My current research focuses on risk factors for type 2 diabetes in American Indians. Type 2 diabetes is an endocrine disorder characterized by insulin resistance, impaired insulin secretion, and hyperglycemia. American Indians and Alaska Natives are disproportionately affected, and have an age-adjusted diabetes prevalence more than twice that of non-Hispanic whites. Both genetic and environmental factors may underlie this disparity. I was recently awarded funds from the National Institutes of Health National Center for Research Resources to cover direct costs of a 5-year investigation of the genetic and environmental risk factors for type 2 diabetes in American Indians in Oklahoma (NIH NCRR Grant Number 1P20RR024215-01). I am PJI (Promising Junior Investigator) of this study, which is included in the Centers of Biomedical Research Excellence (COBRE) project "Mentoring Diabetes Research in Oklahoma" directed by Jian-Xing Ma of the University of Oklahoma Health Sciences Center.
In my study, I will use statistical genetics methods and genetic, medical, and lifestyle information from families to 1) estimate the relative contribution of genetic and environmental factors and their interactions to variation in diabetes-related phenotypes; 2) estimate genetic and environmental correlations between the phenotypes; and 3) conduct genome-wide linkage scans to identify genomic regions including QTLs contributing to phenotype variation. Based on the linkage results, I will use published databases to identify candidate genes for diabetes risk. My goal is to identify genetic and environmental risk factors for type 2 diabetes that are of use in the development of culturally appropriate intervention and treatment strategies.
Whereas there has been considerable interest in identifying risk factors for diabetes in American Indians, my study is significant in its focus on Oklahoma populations. Our current understanding of diabetes risk in American Indians is based largely on investigations of Pima and Tohono O'odham Indians in Arizona. I expect Oklahoma populations to share some risk factors with Arizona populations. However, due to the complex etiology of diabetes and the genetic, cultural, and environmental differences between the populations, I anticipate that factors not identified in Arizona populations will contribute significantly to diabetes risk in Oklahoma groups. I also expect differences between populations in the relative effect sizes of shared risk factors. Conversely, factors identified in Oklahoma groups may contribute to diabetes risk in other populations, including other American Indian populations. My study also provides an opportunity to replicate QTLs identified in the Pima and other populations.
I am also investigating the genetic and environmental factors that contribute to type 2 diabetes in families affected by systemic lupus erythematosus (SLE), an autoimmune disorder. In this research, I use statistical genetics methods including multivariate genome-wide linkage scans to examine genetic and environmental correlations between SLE and diabetes phenotypes, to test for gene-gene and genotype-by-environment interactions, and to localize QTLs influencing type 2 diabetes. The identification of type 2 diabetes risk factors in SLE patients is a major concern due to the contribution of diabetes to cardiovascular disease risk. Cardiovascular disease is a major cause of death in SLE patients.
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Last update: 12
January 2008
© 1995-2008 Diane M. Warren
© 1995-2008 Diane M. Warren