Ida J. Spruill

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

Three Novel mtDNA Restriction Site Polymorphisms Allow Exploration of Population Affinities of African Americans

To develop informative tools for the study of population affinities in African Americans, we sequenced the hypervariable segments I and II (HVS I and HVS II) of mitochondrial DNA (mtDNA) from 96 Sierra Leoneans; European Americans; rural, Gullah-speaking African Americans; urban African Americans living in Charleston, South Carolina; and Jamaicans. We identified single nucleotide polymorphisms (SNPs) exhibiting ethnic affinities, and developed restriction endonuclease tools to screen these SNPs. Here we show that three HVS restriction site polymorphisms (RSPs), EcoRV, FokI, and MfeI, exhibit appreciable differences in frequency (average d = 0.4165) between putative African American parental populations (i.e., extant Africans living in Sierra Leone and European Americans). Estimates of European American mtDNA admixture, calculated from haplotypes composed of these three novel RSPs, show a cline of increasing admixture from Gullah-speaking African American (m = 0.0300) to urban Charleston African American (m = 0.0689) to West Coast African American (m = 0.1769) populations. This haplotype admixture in the Gullahs is the lowest recorded to date among African Americans, consistent with previous studies using autosomal markers. These RSPs may become valuable new tools in the study of ancestral affinities and admixture dynamics of African Americans.

Genome-wide linkage scan in Gullah-speaking African American families with type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR).

OBJECTIVE—The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR). RESEARCH DESIGN AND METHODS—We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach. RESULTS—Linkage peaks on chromosome 14 at 123–124 cM were detected for type 2 diabetes (logarithm of odds [LOD] 2.10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44–45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51) and chromosome 3 at 121.0 cM (LOD 1.61). CONCLUSIONS—This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7.

Enhancing recruitment of African-American families into genetic research: lessons learned from Project SuGar

Despite some recruitment success in biomedical research among minorities, participation by African-American families into research, specifically genetic research, is lower than Caucasian families (Bowen and Penchaszadeh Community Genet 11:189–190, 2008). Such low participation rates by African-Americans prevent the exploration of specific ethnic differences in patterns of diseases and diminish the identification of specific disease risks among ethnic groups (Bowen and Penchaszadeh Community Genet 11:189–190, 2008). Although African-Americans are heterogeneous, few studies exist to describe effective recruitment strategies across diverse African-American populations, and even fewer studies share effective strategies for the enrollment of African-American families into genetic research. A process evaluation of recruitment strategies used by Project SuGar (a community-based genetic research study focusing on families affected by type 2 diabetes) to enroll African-American families into genetic research was conducted. Our goal was to enroll 400 affected African-American families, and our results yielded 672 families, (n = 672). Our success can be attributed to the formation of a Citizen Advisory Committee, recruitment style, flexible protocol, and formal agreement with community health centers. We found that African-American families will participate in research and that providing tangible benefits to the community and utilizing a sense of patience can enhance positive recruitment results. Data from this study may be used to recruit geographically isolated families into genetic research.

Views of Black Nurses toward Genetic Research and Testing

PURPOSE To describe views and beliefs that Black nurses hold regarding several conceptual areas of genetic research and testing. DESIGN Data were generated using a descriptive, cross-sectional design. The sample consisted of 384 Black nurses attending the 2009 annual conference of the National Black Nurses Association in Las Vegas, Nevada. METHODS The chi-squared test was used to evaluate group differences by education level, functional area, age, and gender. FINDINGS One half of the Black nurses surveyed believed the potential for the discriminative misuse of genetic information against minority populations exists. However, 84% of these nurses believed the possibility of information misuse should not be used as a barrier to participation in genetic research and testing by the Black populace. CONCLUSIONS Black nurses expressed concerns about the potential for discriminatory use of genetic information gleaned from research and testing. Yet, Black nurses recognize the importance of racial-ethnic minority participation in genetic research and testing. CLINICAL RELEVANCE Participation in genetic research and testing by diverse populations will provide opportunities to improve the healthcare delivery system and aid the eradication of health disparities. More research is needed to clarify factors that contribute to the bifurcation of importance for participation, reluctance to participate, and what interventions might reduce reluctance.

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR).

We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 ± 0.14). Mean LDL particle size and small LDL particle concentration (−0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration.jlr Our results suggest a significant genetic contribution to multiple lipoprotein subclasses studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration.

African Americans’ Culturally Specific Approaches to the Management of Diabetes:

Spirituality is an important multidimensional cultural resource and coping strategy used by many African Americans for managing chronic diseases such as diabetes. Yet, few studies examine meaning and interpretation of colloquial terms frequently used for coping within the context of a community culture. We designed an interpretive qualitative study to gain a deeper understanding of a colloquial phrase, “I ain’t claiming it,” used among Project SuGar research participants when discussing diabetes. Thematic analysis revealed two major themes, Acknowledgment and Denial, as coping mechanisms through an active or passive relationship with God. Sub-theme of acknowledgment was presented as front seat driver and sub-theme for denial of the disease presented as back seat driver. These meanings encompass a range of culturally specific coping strategies for self-management that health providers should consider and implement as part of providing patient-centered care to enhance better outcome strategies.

A Community-Engaged Assessment of Barriers and Facilitators to Rapid Stroke Treatment

Treatment for acute ischemic stroke must be initiated within hours of stroke symptom onset, and the sooner it is administered, the better. In South Carolina, 76% of the population can access expert stroke care, and rural hospitals may provide specialized treatment using telemedicine, but many stroke sufferers seek care too late to achieve full benefit. Using a community-engaged approach in a southern rural community, we explored barriers and facilitators to early stroke care and implications for improvement. The Community-Engaged Assessment to facilitate Stroke Elimination (CEASE) study was guided by a community advisory group to ensure community centeredness and local relevance. In a qualitative descriptive study, eight focus groups were conducted including 52 individuals: recent stroke survivors, family members, emergency medical personnel, hospital emergency department staff, primary care providers, and community leaders. From analysis of focus group transcripts came six themes: lack of trust in healthcare system and providers; weak relationships fueled by poor communication; low health literacy; financial limitations related to health care; community-based education; and faith as a message of hope. A hierarchy model for improving early community-based stroke care was developed through consensus dialogue by community representatives and the research team. This model can be used to inform a community-partnered, stakeholder-informed intervention to improve stroke care in a rural southern community with the goal of improving stroke education, care, and outcome.

Cardiovascular risk in Gullah African Americans with high familial risk of type 2 diabetes mellitus: project SuGAR.

Objectives To determine the prevalence of cardiovascular disease, levels of cardiovascular risk factors, and extent of preventive care in Gullah African Americans with a high familial risk of type 2 diabetes mellitus. Methods Between 1995 and 2003, 1321 Gullah African Americans with a high prevalence of diabetes mellitus from the South Carolina Sea Islands consented to and enrolled in the Sea Islands Genetic African American Registry (Project SuGAR). A cross-sectional analysis of cardiometabolic risk, preventive care, and self-reported cardiovascular disease was conducted. Results Cardiometabolic risk factor levels were high and vascular disease was prevalent. Among the subjects with diabetes mellitus, the mean disease duration was 10.5 years; approximately one-third reported reduced vision or blindness; and >80% reported numbness, pain, or burning in their feet. Preventive diabetes care was limited, with <60%, <25%, and <40% seeing an ophthalmologist, podiatrist, and dentist, respectively, within the past year. Only 54.4% of women and 39.3% of men reported daily glucose monitoring. Conclusions As the largest existing study of Gullah individuals, our study offers insight into not only the level of cardiovascular risk in this population but also the pathophysiological mechanisms central to ancestral differences in cardiometabolic risk in the broader African American population.

Health disparities in genomics and genetics.

Disparities or inequities in health refer to sociodemographic group differences in the distribution of disease, health outcomes, or access to health care [1]. In order to eliminate health disparities, more efforts are needed to address social issues directly contributing to the healthy inequities observed across racial and ethnic groups. With broad support from many federal agencies, alleviating health disparities in the United States remains a goal of Healthy People 2010 [2]. However, genetic research also has a significant role to play in alleviating and understanding disparities. With tremendous advances in technology and increased investigation into human genetic variations, genomics is poised to play a valuable role in bolstering efforts to find new treatments and preventions for chronic conditions that disparately affect certain ethnic groups. The recent statement regarding the future of genomics from the National Human Genome Research Institute (NHGRI) [3] indicated that the need to develop genome-based tools to address health disparities remains a “grand challenge”. The statement acknowledges that social and economic factors contribute significantly to disparities but nevertheless assert the need for extensive research to better understand the contribution of genetics.