Discerning the ancestry of European Americans in genetic association studies.
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ABSTRACT:
SUBMITTER: Price AL
PROVIDER: S-EPMC2211542 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry.
| S-EPMC4289685 | biostudies-literature
Project description:Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.
| S-EPMC7547691 | biostudies-literature
Project description:BackgroundFamily history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.MethodsIndividual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.ResultsMean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.ConclusionsMean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
| S-EPMC3313995 | biostudies-literature
Project description:A recent genome-wide association study in a German population and two subsequent studies in European populations found that a non-synonymous single-nucleotide polymorphism (SNP), rs1049550, within the annexin A11 (ANXA11) gene was associated with susceptibility to sarcoidosis. We sought to identify additional ANXA11 variants independently associated with sarcoidosis, determine whether any sarcoidosis-associated ANXA11 variants were associated with chest radiographic phenotypes, and explore human leukocyte antigen (HLA) SNP-SNP interactions with ANXA11. A total of 209 SNPs spanning 100 kb including the 5' promoter, coding, and 3' untranslated regions of ANXA11 were genotyped for 1689 sarcoidosis cases and 1252 controls. After adjustment for rs1049550, two additional novel ANXA11 sarcoidosis associations were identified only in African Americans--rs61860052 (odds ratio (OR)=0.62; 95% confidence interval (CI)=0.40-0.97) and rs4377299 (OR=1.31; 95% CI=1.06-1.63). These associations were more pronounced in radiologically-classified Scadding stage IV sarcoidosis cases. We also identified a significant SNP-SNP interaction between rs1049550 and a sarcoidosis risk SNP (rs9268839) near the HLA-DRA locus. This further genetic dissection of ANXA11 may provide additional insight into the immune dysregulation characteristic of sarcoidosis pathophysiology.
| S-EPMC3595044 | biostudies-literature
Project description:Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR≥0.4 ), and ≥15% NAA (AMR≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10-4 ; 11p11.12, p = 7.0 × 10-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10-6 ) in 7q21.3. Among AMR≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10-4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.
| S-EPMC6785354 | biostudies-literature
Project description:BackgroundPoor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited.MethodsWe used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography-tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth.ResultsAfter adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (β = 0.16, se = 1.07, p-value = 0.024) and depression scores (β = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (β = -0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05).ConclusionWhile the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.
| S-EPMC10865309 | biostudies-literature
Project description:Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI?15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10(-6). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.
| S-EPMC3498243 | biostudies-literature
Project description:Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs10516487, within the B-cell gene BANK1 and systemic lupus erythematosus (SLE) as a consequence of a genome wide association study of this disease in European and Argentinean populations. In a bid for replication, we examined the effects of the R61H non-synonymous variant with respect to SLE in our genotyped American cohorts of European and African ancestry. Utilizing data from our ongoing genome-wide association study in our cohort of 178 Caucasian SLE cases and 1808 Caucasian population-based controls plus 148 African American (AA) SLE cases and 1894 AA population-based controls we investigated the association of the previously described non-synonymous SNP at the BANK1 locus with the disease in the two ethnicities separately. Using a Fisher's exact test, the minor allele frequency (MAF) of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR) of 0.64 (95% CI 0.49-0.85; one-sided p = 7.07 × 10(-4)). Furthermore, the MAF of rs10516487 in the AA cases was 18.7% while it was 23.3% in AA controls, yielding a protective OR of 0.75 (95% CI 0.55-1.034; one-sided p = 0.039). The OR of the BANK1 variant in our study cohorts is highly comparable with that reported previously in a South American/European SLE case-control cohort (OR = 0.72). As such, R61H in the BANK1 gene confers a similar magnitude of SLE protection, not only in European Americans, but also in African Americans.
| S-EPMC3681036 | biostudies-literature
Project description:Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent.
| S-EPMC3895491 | biostudies-literature
Project description:European-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrate individual-level genome-wide data from ~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generate a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European Americans are admixed at the subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant in LCT (rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association between LCT and body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
| S-EPMC10630423 | biostudies-literature