Genetic Epidemiology

1. Develop a population-based genetic epidemiology resource for the study of common complex diseases in populations of the African Diaspora. 

Research Activity 

In the short term, the genetic epidemiology unit is developing a population-based resource for the NHGC at Howard to enhance the ability of center’s investigators to compete for external funds. This resource will include 600 multi-generational pedigrees (300 African Americans and 300 West Africans) with at least 5 persons per families. 

In the long term we will develop an international population repository of 1,500 multi-generational pedigrees of African origin populations with study sites in West Africa (Ghana and Nigeria; n=500 families), the Caribbean (Jamaica and Barbados; n=500 families) and the US (Washington, DC and Maryland; n=500 families) for a minimum sample size of 7,500 individuals.

To this end the Genetic Epidemiology unit has received initial funding to develop a population-based resource of 600 multi-generational African American (n=300 families and 1,500 persons) and West African (n=300 families and 1,500 persons) pedigrees to study the genetic epidemiology of diabetes, hypertension and obesity. The African Americans families will be enrolled from Washington, DC and Maryland communities. The West African families will be enrolled from Nigeria and Ghana. The manual of operation is complete and fieldwork is scheduled to start in the US in December of this year. In addition, we are in the process of securing funding to expand the study to the black Caribbean nations of Jamaica and Barbados.

Genetic diversity of African people 

An obvious benefit of the human Genome project is bound to be a better understanding of human evolutionary history. By employing recent molecular tools we can now study polymorphic markers (SNPs and STRs) on different chromosomes to understand the degree of similarity or divergence between African populations; a process that will have profound implication for blacks in the Western Hemisphere whose ancestors are the survivals of the forced migration out of the west and southwest coast of Africa.  Different groups have attempted to study these issues with varying success partly due to poorly developed hypotheses and the inherent biases ever present in the quest to understanding the origin of human civilization.  Proposed population-based resources will undoubtedly facilitate the full participation of investigators at the genome center at Howard University. A major goal of this genome center is to lead the discussion on genetic variation in populations of the African Diaspora.  

2.   Develop a major focus in the ethical issues related to the process of obtaining informed consent in genetic epidemiology studies at the national and international levels. 

To this end Dr. Rotimi is a Co-PI on a new initiative (an RO1 grant) titled “Informed Consent and Concepts of Race in Genetic Research” with Dr. Patricia Marshall as the Principal Investigator. This study hopes to advance our understanding of the ethical dimensions of genetic research in diverse populations. The process of obtaining informed consent provides the focus for ethical exchange between investigators and study participants. This study will take advantage of this social interaction to explore ethical issues associated with the implementation of collaborative international genetic research. In addition, broad issues of society will be addressed by examining how genetic identity and race are conceptualized in both the lay and professional communities. 

Dr. Rotimi’s participation in several national and international conferences addressing ethical issues in biomedical research is a demonstration of his commitment to this important area of research and community inclusion. He was a member of an international panel in a recently completed conference titled “First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research” conducted by the Fogarty International Center. 

3.   Foster collaboration between the NHGC at Howard University and investigators in other minority institutions.

Commitment to this objective is evident in recent collaborations with Jackson Heart Study (JHS), Jackson, Mississippi and Morehouse School of Medicine, Atlanta, Georgia.  The Genetic Epidemiology unit is actively involved in the development of the research protocol for the family study component of the JHS. This component of the JHS is designed to detect genes influencing risk factors for a variety of heart, lung and blood disorders.  To this end, family enrollment is based on a random ascertainment strategy.  The Family study is nested within the JHS population-based sample, such that each participant eligible to participate in the JH cohort study is a potential proband (initial family contact) for the family study.  This will ensure that results obtained from the Family Study are generalizable to the greater JHS community. 

Another major objective of the NHGC at Howard University and the JHS collaboration is to increase minority participation in the national human genome project. To this end, Howard University investigators will conduct several training section in genetic epidemiology and ethical issues in biomedical research in Jackson, MS. Participants will include faculty members, graduate and undergraduate students in Jackson State University, Tougaloo College and the University of Mississippi Medical Center.  In addition, JHS investigators and students will have the opportunity to visit Howard University.   

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4.  Train minority investigators and Students at Howard University. 

An important reason underlying Dr. Rotimi’s move from Loyola University in Chicago is to increase the number of minority investigators participating in genetic epidemiology studies. The long-term goal is to maintain on staff at, all times, at least two post-doctoral fellows who will be interested in developing career in genetic epidemiology common complex diseases. To this end, the genetic epidemiology unit current has to fellows (Drs. Olufemi Adegoke and Gary Ellison) who are pursuing varying interests in the unit. Dr. Adegoke, an MD from Nigeria, also has a PhD in Epidemiology and is current the coordinator of our diabetes study in West Africa.  Dr. Ellison, with a PhD in Epidemiology, is coordinating our obesity grant and actively involved in the training of field staff for the Jackson Heart Study, Jackson, MS. He recently demonstrated a growing independence by developing a research proposal as a supplement to Dr. Rotimi’s R01 grants on the genetic of obesity in blacks. His grant received excellent score and has been funded for fours.  In addition, his work evaluating the association between a quantitative trait locus on chromosome 2 and obesity-related phenotypes was recently accepted for present in the next North America Association for the Study of Obesity later this month in Long Beach, California. We hope to continue to attract young bright minority investigator to continue these efforts. 

5.   Revive summer training programs in epidemiology, biostatistics and research protocol development in West Africa. 

This program was developed by Dr. Rotimi during his tenure at Loyola University in Chicago and was funded for three years by the Loyola, CDC and USAID. The possibility of future funding is being discussed with the Fogarty Institute at NIH. While activity, this program created the only opportunity for many West African physicians and other health care workers to be exposed to course in research protocol development and the use of computer technology in the design and analysis of data.

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CURRENT FUNDED RESEARCH ACTIVITIES 

Genetic epidemiology unit of NHGC currently has NIH funding to study the Genetic and environmental determinants of type 2 diabetes, obesity, hypertension and associated risk factors in populations of the African Diaspora.  Since joining Howard University faculty in July of last year (1999), Dr. Rotimi has received funding for five independent projects including two R01 grants (genetics of obesity - PI; Informed consent and the concept of race – Co-PI). 

A.        Genetics of Obesity 

Obesity and its complications are more common among blacks in the US than whites.  The social and biological determinants of this increased risk are poorly understood. Since the prevalence of obesity remains low in West Africa, a founder population for US blacks, contrasts between these populations allow one to test whether the high rate of obesity among African Americans is a result of exposure to higher levels of environmental risk factors, an increased genetic susceptibility, or an interaction between adverse environments and deleterious genes. 

Heritable factors are thought to contribute 20-40% of obesity risk, although to date no large scale studies have examined the molecular basis for this phenomenon among populations of African descent.  Association and linkage analysis now provide powerful tools for defining genetic risk factors and substantial progress is being made in the genetics of obesity.  Large-scale family studies thus become an important priority in the effort to identify the determinants of obesity.

This study builds on an on-going family study in the US and West Africa, we propose to examine the genetics of obesity in blacks.  Familial aggregation and patterns of inheritance will provide indirect evidence on the role of inheritance.  The molecular basis for susceptibility will be examined with association and linkage analysis using reported candidate loci/regions.  Finally, by examining the impact of variant alleles of these candidate genes among genetically related populations in contrasting environments, evidence of potential gene-environment interactions will be sought.   

Specific Aims: 

1. Determine whether the familial aggregation of obesity is influenced by environmental factors by contrasting the distribution of familial correlations of obesity in Maywood, IL, and Idere, Nigeria. 

2. Use segregation analysis to determine the mode of inheritance of the obesity traits in African Americans and Nigerians. 

3. Use association and linkage analyses to study the molecular basis of obesity in these populations with the candidate gene approach.

To accomplish these aims we will: 

1. Use an established collaboration to identify a sample of 400 nuclear families with 4 or more members from Maywood, IL, and 400 families with 4 or more members from Idere, Nigeria, for a total of 800 families and 3,200 individuals.

2. Measure fat mass (FM), fat-free mass (FFM), percent body fat (PBF), weight, height, body mass index (BMI), waist and hip circumferences, resting metabolic rate (RMR), leptin, insulin and glucose in all participants from Maywood and Nigeria.

3. Model the pattern of inheritance of obesity traits in Maywood and Nigeria and assess potential differences observed in