Browsing by Subject "African Continental Ancestry Group"
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Item An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry(Nature Publishing Group, 2017-12) Meyers, JL; Zhang, J; Wang, JC; Su, J; Kuo, SI; Kapoor, M; Wetherill, L; Bertelsen, S; Lai, D; Salvatore, JE; Kamarajan, C; Chorlian, D; Agrawal, A; Almasy, L; Bauer, L; Bucholz, KK; Chan, G; Hesselbrock, V; Koganti, L; Kramer, J; Kuperman, S; Manz, N; Pandey, A; Seay, M; Scott, D; Taylor, RE; Dick, DM; Edenberg, HJ; Goate, A; Foroud, T; Porjesz, B; Medical and Molecular Genetics, School of MedicineFast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.Item Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.(IOS Press, 2015) Kim, Sungeun; Nho, Kwangsik; Ramanan, Vijay K.; Lai, Dongbing; Foroud, Tatiana M.; Lane, Katie; Murrell, Jill R.; Gao, Sujuan; Hall, Kathleen S.; Unverzagt, Frederick W.; Baiyewu, Olusegun; Ogunniyi, Adesola; Gureje, Oye; Kling, Mitchel A.; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Hendrie, Hugh C.; Saykin, Andrew J.; Department of Radiology and Imaging Sciences, IU School of MedicinePlasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer’s disease (AD) and other dementias. A better understanding of the genetic factors regulating homocysteine levels, particularly in non-white populations, may help in risk stratification analyses of existing clinical trials and may point to novel targets for homocysteine-lowering therapy. To identify genetic influences on plasma homocysteine levels in individuals with African ancestry, we performed a targeted gene and pathway-based analysis using a priori biological information and then to identify new association performed a genome-wide association study. All analyses used combined data from the African American and Yoruba cohorts from the Indianapolis-Ibadan Dementia Project. Targeted analyses demonstrated significant associations of homocysteine and variants within the CBS (Cystathionine beta-Synthase) gene. We identified a novel genome-wide significant association of the AD risk gene CD2AP (CD2-associated protein) with plasma homocysteine levels in both cohorts. Minor allele (T) carriers of identified CD2AP variant (rs6940729) exhibited decreased homocysteine level. Pathway enrichment analysis identified several interesting pathways including the GABA receptor activation pathway. This is noteworthy given the known antagonistic effect of homocysteine on GABA receptors. These findings identify several new targets warranting further investigation in relation to the role of homocysteine in neurodegeneration.Item Global skin colour prediction from DNA(Springer Berlin Heidelberg, 2017) Walsh, Susan; Chaitanya, Lakshmi; Breslin, Krystal; Muralidharan, Charanya; Bronikowska, Agnieszka; Pospiech, Ewelina; Koller, Julia; Kovatsi, Leda; Wollstein, Andreas; Branicki, Wojciech; Liu, Fan; Kayser, Manfred; Biology, School of ScienceHuman skin colour is highly heritable and externally visible with relevance in medical, forensic, and anthropological genetics. Although eye and hair colour can already be predicted with high accuracies from small sets of carefully selected DNA markers, knowledge about the genetic predictability of skin colour is limited. Here, we investigate the skin colour predictive value of 77 single-nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with human pigmentation using 2025 individuals from 31 global populations. We identified a minimal set of 36 highly informative skin colour predictive SNPs and developed a statistical prediction model capable of skin colour prediction on a global scale. Average cross-validated prediction accuracies expressed as area under the receiver-operating characteristic curve (AUC) ± standard deviation were 0.97 ± 0.02 for Light, 0.83 ± 0.11 for Dark, and 0.96 ± 0.03 for Dark-Black. When using a 5-category, this resulted in 0.74 ± 0.05 for Very Pale, 0.72 ± 0.03 for Pale, 0.73 ± 0.03 for Intermediate, 0.87±0.1 for Dark, and 0.97 ± 0.03 for Dark-Black. A comparative analysis in 194 independent samples from 17 populations demonstrated that our model outperformed a previously proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White, comparable at the intermediate level of 0.63 and 0.62, respectively, and a large increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the chosen DNA markers and prediction model, particularly the 5-category level; allow skin colour predictions within and between continental regions for the first time, which will serve as a valuable resource for future applications in forensic and anthropologic genetics.Item Prader-Willi syndrome: are there population differences?(Wiley, 1982-11) Butler, Merlin G.; Weaver, David D.; Meaney, F. John; Medical and Molecular Genetics, School of MedicineA 15 1/2-year-old black female with features consistent with the Prader-Willi syndrome is reported. This is the second case report of a black individual and the first case of a black female with the Prader-Willi syndrome. There is an apparent paucity of blacks reported with this condition. Whether this difference is a true difference or represents under-reporting is not known. We urge reporting of individuals representing other racial groups with this disorder and suggest population studies to determine the incidence as well as the true population difference in the Prader-Willi syndrome.Item Racial and Ethnic Differences in Total Knee Arthroplasty in the Veterans Affairs Health Care System, 2001-2013(Wiley, 2017-08) Hausmann, Leslie R.M.; Brandt, Cynthia A.; Carroll, Constance M.; Fenton, Brenda T.; Ibrahim, Said A.; Becker, William C.; Burgess, Diana J.; Wandner, Laura D.; Bair, Matthew J.; Goulet, Joseph L.; Medicine, School of MedicineOBJECTIVE: To examine black-white and Hispanic-white differences in total knee arthroplasty from 2001 to 2013 in a large cohort of patients diagnosed with osteoarthritis (OA) in the Veterans Affairs (VA) health care system. METHODS: Data were from the VA Musculoskeletal Disorders cohort, which includes data from electronic health records of more than 5.4 million veterans with musculoskeletal disorders diagnoses. We included white (non-Hispanic), black (non-Hispanic), and Hispanic (any race) veterans, age ≥50 years, with an OA diagnosis from 2001-2011 (n = 539,841). Veterans were followed from their first OA diagnosis until September 30, 2013. As a proxy for increased clinical severity, analyses were also conducted for a subsample restricted to those who saw an orthopedic or rheumatology specialist (n = 148,844). We used Cox proportional hazards regression to examine racial and ethnic differences in total knee arthroplasty by year of OA diagnosis, adjusting for age, sex, body mass index, physical and mental diagnoses, and pain intensity scores. RESULTS: We identified 12,087 total knee arthroplasty procedures in a sample of 473,170 white, 50,172 black, and 16,499 Hispanic veterans. In adjusted models examining black-white and Hispanic-white differences by year of OA diagnosis, total knee arthroplasty rates were lower for black than for white veterans diagnosed in all but 2 years. There were no Hispanic-white differences regardless of when diagnosis occurred. These patterns held in the specialty clinic subsample. CONCLUSION: Black-white differences in total knee arthroplasty appear to be persistent in the VA, even after controlling for potential clinical confounders.Item Response to "is high prorenin level related to relative aldosterone excess?"(Oxford University Press, 2013-02) Tu, Wanzhu; Eckert, George J.; Pratt, J. Howard; Danser, A.H. Jan; Department of Medicine, IU School of MedicineComment in: Is high prorenin levels related to relative aldosterone excess? [Am J Hypertens. 2013] Comment on: Plasma levels of prorenin and renin in blacks and whites: their relative abundance and associations with plasma aldosterone concentration. [Am J Hypertens. 2012]Item Sister-chromatid exchange in 4 human races(Elsevier, 1981-09) Butler, Merlin G.; Department of Medical and Molecular Genetics, IU School of MedicineThe frequencies of sister-chromatid exchanges (SCE) were investigated in lymphocytes in 32 normal adult individuals of both sexes with no interracial familial backgrounds from Caucasian, American black, oriental and native American races. There was no significant difference in the average frequency of SCEs in the 4 races.Item Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago(Alcohol Research Documentation, 2014-09) Jaime, Lazara Karelia Montane; Shafe, Samuel; Liang, Tiebing; Wills, Derek N.; Berg, Greta I.; Ehlers, Cindy L.; Department of Medicine, IU School of MedicineOBJECTIVE: Level of response to alcohol has been associated with risk of alcohol dependence in a number of ethnic groups. In the present study, subjective and objective responses to alcohol were evaluated in Indo-Trinidadians (Indo-T) and Afro-Trinidadians (Afro-T). Associations of alcohol dehydrogenase polymorphisms with response to alcohol, using the Subjective High Assessment Scale (SHAS), and breath alcohol concentrations (BrAC) were tested. METHOD: Regular male drinkers without alcohol dependence (n = 112) ages 18-25 years participated in alcohol challenge sessions consisting of placebo and two doses of alcohol (target BrAC: 0 g/dl for placebo, .04 g/dl low dose, and .08 g/dl high dose) and genotyped for variants in ADH1B*3 and ADH1C*2. RESULTS: Indo-T had significantly higher BrAC, pulse rates, and cortisol levels when compared with Afro-T but did not have significantly higher SHAS values. Higher responses on the SHAS items muddle/confused and nauseated were significantly associated with the presence of at least one ADH1B*3 allele following the high dose of alcohol in Afro-T. Indo-T with at least one ADH1C*2 allele displayed significantly different Drug × Time interactions for the SHAS item effects of alcohol at the low dose and for the SHAS items clumsy, muddle/confused, effects of alcohol, floating, drunk, and total at the high dose from Indo-T with two ADH1C*1 alleles. CONCLUSIONS: This is the first study that has investigated individual sensitivity to alcohol in a Caribbean population and in people of East Indian descent. Indo-T with at least one ADH1C*2 allele may be at higher risk for heavy drinking by feeling less of the effects of alcohol, including nausea. In Afro-T, having at least one ADH1B*3 allele appears to exert a protective effect by enhancing the unpleasant effects of alcohol, such as nausea and confusion.Item Vascular considerations in glaucoma patients of African and European descent(Wiley Blackwell (Blackwell Publishing), 2014-08) Huck, Andrew; Harris, Alon; Siesky, Brent; Kim, Nathaniel; Muchnik, Michael; Kanakamedala, Priyanka; Amireskandari, Annahita; Abrams-Tobe, Leslie; Department of Ophthalmology, IU School of MedicineGlaucoma is the leading cause of blindness in individuals of African descent (AD). While open-angle glaucoma (OAG) disproportionately affects individuals of AD compared with persons of European descent (ED), the physiological mechanisms behind this disparity are largely unknown. The more rapid progression and greater severity of the disease in persons of AD further raise the concern for identifying these underlying differences in disease pathophysiology between AD and ED glaucoma patients. Ocular structural differences between AD and ED patients, including larger optic disc area, cup:disc ratio and thinner corneas, have been found. AD individuals are also disproportionately affected by systemic vascular diseases, including hypertension, cardiovascular disease, stroke and diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk factor for glaucoma, and pilot research is beginning to identify localized ocular vascular differences between AD and ED OAG patients. Given the known systemic vascular deficits and the relationship between glaucoma and ocular blood flow, exploring these concepts in terms of glaucoma risk factors may have a significant impact in elucidating the mechanisms behind the disease disparity in the AD population.Item Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children(Endocrine Society, 2016-04) Ferira, Ashley J.; Laing, Emma M.; Hausman, Dorothy B.; Hall, Daniel B.; McCabe, George P.; Martin, Berdine R.; Hill Gallant, Kathleen M.; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.; Medicine, School of MedicineCONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.