Genomic Ancestry of North Africans Supports Back-to-Africa Migrations

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa

A study assessing the association of glycated hemoglobin a1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of asian ancestry

10.1371/journal.pone.0079767PLoS ONE811-POLN

Cross-sectional associations between adipose tissue depots and areal bone mineral density in the UK Biobank imaging study

Summary: The relationship between obesity and osteoporosis is poorly understood. In this study, we assessed the association between adiposity and bone. The fat–bone relationship was dependent on sex, body mass index classification, and menopausal status. Results highlight the importance of accounting for direct measures of adiposity (beyond BMI) and menopause status. Introduction: Assess the relationship between direct measures of adiposity (total body fat mass, visceral adipose tissue, and abdominal subcutaneous adipose tissue) with the whole body and clinically relevant bone sites of the lumbar spine, and femoral neck areal bone mineral density (aBMD) in men and women. Methods: This cross-sectional analysis was conducted utilizing de-identified data from the UK Biobank on participants (n = 3674) with available dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) data. Sex-stratified multiple linear regression was used to assess the relationship between adiposity measures and aBMD outcomes, controlling for age, race, total body lean mass (DXA), height, BMI class, physical activity, smoking, menopausal status (women), and hormone use (women). Results: In men, significant interactions were observed between measures of adiposity and BMI on aBMD for the whole body and lumbar spine. Interactions indicated a positive relationship between adiposity and aBMD in men classified as normal weight, but an inverse relationship in men with elevated BMI. In women, significant interactions between adiposity measures and menopausal status were observed primarily for the whole body and femoral neck aBMD bone outcomes which indicated a negative relationship between adiposity and aBMD in premenopausal women, but a positive relationship in postmenopausal women. Conclusion: Total body adiposity, abdominal subcutaneous adipose tissue, and visceral adipose tissue were all significantly associated with aBMD in both men and women. The strength and direction of association were dependent on sex, BMI classification, and menopausal status (women).12 month embargo; published: 06 September 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Leveraging genetic ancestry to study health disparities

Research to understand human genomic variation and its implications in health has great potential to contribute in the reduction of health disparities. Biological anthropology can play important roles in genomics and health disparities research using a biocultural approach. This paper argues that racial/ethnic categories should not be used as a surrogate for sociocultural factors or global genomic clusters in biomedical research or clinical settings, because of the high genetic heterogeneity that exists within traditional racial/ethnic groups. Genetic ancestry is used to show variation in ancestral genomic contributions to recently admixed populations in the United States, such as African Americans and Hispanic/Latino Americans. Genetic ancestry estimates are also used to examine the relationship between ancestry-related biological and sociocultural factors affecting health disparities. To localize areas of genomes that contribute to health disparities, admixture mapping and genome-wide association studies (GWAS) are often used. Recent GWAS have identified many genetic variants that are highly differentiated among human populations that are associated with disease risk. Some of these are population-specific variants. Many of these variants may impact disease risk and help explain a portion of the difference in disease burden among racial/ethnic groups. Genetic ancestry is also of particular interest in precision medicine and disparities in drug efficacy and outcomes. By using genetic ancestry, we can learn about potential biological differences that may contribute to the heterogeneity observed across self-reported racial groups.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes

INTRODUCTION: Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET). RESEARCH DESIGN AND METHODS: This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer's disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models. RESULTS: Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15). CONCLUSIONS: Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Elucidating symptoms of COVID-19 illness in the Arizona CoVHORT: A longitudinal cohort study

Objective To elucidate the symptoms of laboratory-confirmed COVID-19 cases as compared with laboratory-confirmed negative individuals and to the untested general population among all participants who reported symptoms within a large prospective cohort study. Setting and design This work was conducted within the framework of the Arizona CoVHORT, a longitudinal prospective cohort study conducted among Arizona residents. Participants Eligible participants were any individual living in Arizona and were recruited from across Arizona via COVID-19 case investigations, participation in testing studies and a postcard mailing effort. Primary and secondary outcome measures The primary outcome measure was a comparison of the type and frequency of symptoms between COVID-19-positive cases, tested but negative individuals and the general untested population who reported experiencing symptoms consistent with COVID-19. Results Of the 1335 laboratory-confirmed COVID-19 cases, 180 (13.5%) reported having no symptoms. Of those that did report symptoms, the most commonly reported were fatigue (82.2%), headache (74.6%), aches, pains or sore muscles (66.3%), loss of taste or smell (62.8) and cough (61.9%). In adjusted logistic regression models, COVID-19-positive participants were more likely than negative participants to experience loss of taste and smell (OR 12.1; 95% CI 9.6 to 15.2), bone or nerve pain (OR 3.0; 95% CI 2.2 to 4.1), headache (OR 2.6; 95% CI 2.2 to 3.2), nausea (OR 2.4; 95% CI 1.9 to 3.1) or diarrhoea (OR 2.1; 95% CI 1.7 to 2.6). Fatigue (82.9) and headache (74.9) had the highest sensitivities among symptoms, while loss of taste or smell (87.2) and bone or nerve pain (92.9) had the high specificities among significant symptoms associated with COVID-19. Conclusion When comparing confirmed COVID-19 cases with either confirmed negative or untested participants, the pattern of symptoms that discriminates SARS-CoV-2 infection from those arising from other potential circulating pathogens may differ from general reports of symptoms among cases alone. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

High Viremia Is Associated with High Levels of In Vivo Major Histocompatibility Complex Class I Downregulation in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239 ▿ †

Human and simian immunodeficiency viruses (HIV and SIV) downregulate major histocompatibility complex class I (MHC-I) molecules from the surface of infected cells. Although this activity is conserved across viral isolates, its importance in AIDS pathogenesis is not clear. We therefore developed an assay to detect the level of MHC-I expression of SIV-infected cells directly ex vivo. Here we show that the extent of MHC-I downregulation is greatest in SIVmac239-infected macaques that never effectively control virus replication. Our results suggest that a high level of MHC-I downregulation is a hallmark of fast disease progression in SIV infection