Research Priorities for Interventions to Address Health Disparities in Lung Nodule Management: An Official American Thoracic Society Research Statement.

Background: Lung nodules are common incidental findings, and timely evaluation is critical to ensure diagnosis of localized-stage and potentially curable lung cancers. Rates of guideline-concordant lung nodule evaluation are low, and the risk of delayed evaluation is higher for minoritized groups. Objectives: To summarize the existing evidence, identify knowledge gaps, and prioritize research questions related to interventions to reduce disparities in lung nodule evaluation. Methods: A multidisciplinary committee was convened to review the evidence and identify key knowledge gaps in four domains: 1) research methodology, 2) patient-level interventions, 3) clinician-level interventions, and 4) health system-level interventions. A modified Delphi approach was used to identify research priorities. Results: Key knowledge gaps included 1) a lack of standardized approaches to identify factors associated with lung nodule management disparities, 2) limited data evaluating the role of social determinants of health on disparities in lung nodule management, 3) a lack of certainty regarding the optimal strategy to improve patient-clinician communication and information transmission and/or retention, and 4) a paucity of information on the impact of patient navigators and culturally trained multidisciplinary teams. Conclusions: This statement outlines a research agenda intended to stimulate high-impact studies of interventions to mitigate disparities in lung nodule evaluation. Research questions were prioritized around the following domains: 1) need for methodologic guidelines for conducting research related to disparities in nodule management, 2) evaluating how social determinants of health influence lung nodule evaluation, 3) studying approaches to improve patient-clinician communication, and 4) evaluating the utility of patient navigators and culturally enriched multidisciplinary teams to reduce disparities.

Amplifying Their Voices: Advice, Guidance, and Perceived Value of Cancer Biobanking Research Among an Older, Diverse Cohort.

The use of biobanks may accelerate scientists' chances of developing cures and treatments that are tailored to individuals' biological makeup-a function of the precision medicine movement. However, given the underrepresentation of certain populations in biobanks, the benefits of these resources may not be equitable for all groups, including older, multi-ethnic populations. The objective of this study was to better understand older, multi-ethnic populations' (1) perceptions of the value of cancer biobanking research, (2) study design preferences, and (3) guidance on ways to promote and increase participation. This study was designed using a community-based participatory research (CBPR) approach and involved eight FGDs with 67 older (65-74 years old) black and white residents from Baltimore City and Prince George's County, MD. FGDs lasted between 90 and 120 min, and participants received a $25 Target gift card for their participation. Analysis involved an inductive approach in which we went through a series of open and axial coding techniques to generate themes and subthemes. Multiple themes emerged from the FGDs for the development of future cancer-related biobanking research including (1) expectations/anticipated benefits, (2) biobanking design preferences, and (3) ways to optimize participation. Overall, most participants were willing to provide biospecimens and favored cancer-related biobank. To increase participation of older, diverse participants in biobanking protocols, researchers need to engage older, diverse persons as consultants in order to better understand the value of biobanking research to individuals from the various populations. Scientists should also incorporate suggestions from the community on garnering trust and increasing comfort with study design.

Association of HLA-DRB1∗09:01 with tIgE levels among African-ancestry individuals with asthma.

BACKGROUND: Asthma is a complex chronic inflammatory disease of the airways. Association studies between HLA and asthma were first reported in the 1970s, and yet, the precise role of HLA alleles in asthma is not fully understood. Numerous genome-wide association studies were recently conducted on asthma, but were always limited to simple genetic markers (single nucleotide polymorphisms) and not complex HLA gene polymorphisms (alleles/haplotypes), therefore not capturing the biological relevance of this complex locus for asthma pathogenesis. OBJECTIVE: To run the first HLA-centric association study with asthma and specific asthma-related phenotypes in a large cohort of African-ancestry individuals. METHODS: We collected high-density genomics data for the Consortium on Asthma among African-ancestry Populations in the Americas (N = 4993) participants. Using computer-intensive machine-learning attribute bagging methods to infer HLA alleles, and Easy-HLA to infer HLA 5-gene haplotypes, we conducted a high-throughput HLA-centric association study of asthma susceptibility and total serum IgE (tIgE) levels in subjects with and without asthma. RESULTS: Among the 1607 individuals with asthma, 972 had available tIgE levels, with a mean tIgE level of 198.7 IU/mL. We could not identify any association with asthma susceptibility. However, we showed that HLA-DRB1∗09:01 was associated with increased tIgE levels (P = 8.5 × 10-4; weighted effect size, 0.51 [0.15-0.87]). CONCLUSIONS: We identified for the first time an HLA allele associated with tIgE levels in African-ancestry individuals with asthma. Our report emphasizes that by leveraging powerful computational machine-learning methods, specific/extreme phenotypes, and population diversity, we can explore HLA gene polymorphisms in depth and reveal the full extent of complex disease associations.

Access to internet, smartphone usage, and acceptability of mobile health technology among cancer patients.

PURPOSE: The use of mobile health (mHealth) technologies to augment patient care enables providers to communicate remotely with patients enhancing the quality of care and patient engagement. Few studies evaluated predictive factors of its acceptance and subsequent implementation, especially in medically underserved populations. METHODS: A cross-sectional study of 151 cancer patients was conducted at an academic medical center in the USA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients' current and desired use of mHealth technology for healthcare services. RESULTS: Of the 151 participants, 35.8% were male and ages ranged from 21 to 104 years. 73.5% of participants currently have daily access to internet, and 68.2% currently own a smartphone capable of displaying mobile applications. Among all participants, acceptability of a daily mHealth application was significantly higher in patients with a college-level degree (OR 2.78, CI95% 1.25-5.88) and lower in patients > 80 years of age (OR 0.05, CI95% 0.01-0.23). Differences in acceptability when adjusted for current smartphone use and daily access to internet were nonsignificant. Among smartphone users, the desire to increase cancer knowledge was associated with a higher likelihood of utilizing a mHealth application (OR 261.53, CI95% 10.13-6748.71). CONCLUSION: The study suggests that factors such as age, educational achievement, and access to internet are significant predictors of acceptability of a mHealth application among cancer patients. Healthcare organizations should consider these factors when launching patient engagement platforms.

A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.

Short-acting ß2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Breastfeeding associated with higher lung function in African American youths with asthma.

OBJECTIVE: In the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV1) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma. METHODS: As part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV1% predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations. RESULTS: Prevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only. CONCLUSION: Breastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Effect of Patient Navigation on Breast Cancer Screening Among African American Medicare Beneficiaries: A Randomized Controlled Trial.

BACKGROUND: There is growing evidence that patient navigation improves breast cancer screening rates; however, there are limited efficacy studies of its effect among African American older adult women. OBJECTIVE: To evaluate the effect of patient navigation on screening mammography among African American female Medicare beneficiaries in Baltimore, MD. DESIGN: The Cancer Prevention and Treatment Demonstration (CPTD), a multi-site study, was a randomized controlled trial conducted from April 2006 through December 2010. SETTING: Community-based and clinical setting. PARTICIPANTS: The CPTD Screening Trial enrolled 1905 community-dwelling African American female Medicare beneficiaries who were ≥65 years of age and resided in Baltimore, MD. Participants were recruited from health clinics, community centers, health fairs, mailings using Medicare rosters, and phone calls. INTERVENTIONS: Participants were randomized to either: printed educational materials on cancer screening (control group) or printed educational materials + patient navigation services designed to help participants overcome barriers to cancer screening (intervention group). MAIN MEASURE: Self-reported receipt of mammography screening within 2 years of the end of the study. KEY RESULTS: The median follow-up period for participants in this analysis was 17.8 months. In weighted multivariable logistic regression analyses, women in the intervention group had significantly higher odds of being up to date on mammography screening at the end of the follow-up period compared to women in the control group (odds ratio [OR] 2.26, 95 % confidence interval [CI]1.59-3.22). The effect of the intervention was stronger among women who were not up to date with mammography screening at enrollment (OR 3.63, 95 % CI 2.09-6.38). CONCLUSION: Patient navigation among urban African American Medicare beneficiaries increased self-reported mammography utilization. The results suggest that patient navigation for mammography screening should focus on women who are not up to date on their screening.

Genetic ancestry influences asthma susceptibility and lung function among Latinos.

BACKGROUND: Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. OBJECTIVE: To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. METHODS: We analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. RESULTS: Native American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively). CONCLUSION: Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos.

Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos.

BACKGROUND: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders. OBJECTIVE: We sought to identify genetic variants associated with IgE levels in Latinos. METHODS: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies. RESULTS: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011). CONCLUSION: We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels.

Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American adults.

PURPOSE: In recent years, colorectal cancer (CRC) screening rates have increased steadily in the USA, though racial and ethnic disparities persist. In a community-based randomized controlled trial, we investigated the effect of patient navigation on increasing CRC screening adherence among older African Americans. METHODS: Participants in the Cancer Prevention and Treatment Demonstration were randomized to either the control group, receiving only printed educational materials (PEM), or the intervention arm where they were assigned a patient navigator in addition to PEM. Navigators assisted participants with identifying and overcoming screening barriers. Logistic regression analyses were used to assess the effect of patient navigation on CRC screening adherence. Up-to-date with screening was defined as self-reported receipt of colonoscopy/sigmoidoscopy in the previous 10 years or fecal occult blood testing (FOBT) in the year prior to the exit interview. RESULTS: Compared with controls, the intervention group was more likely to report being up-to-date with CRC screening at the exit interview (OR 1.55, 95 % CI 1.07-2.23), after adjusting for select demographics. When examining the screening modalities separately, the patient navigator increased screening for colonoscopy/sigmoidoscopy (OR 1.53, 95 % CI 1.07-2.19), but not FOBT screening. Analyses of moderation revealed stronger effects of navigation among participants 65-69 years and those with an adequate health literacy level. CONCLUSIONS: In a population of older African Americans adults, patient navigation was effective in increasing the likelihood of CRC screening. However, more intensive navigation may be necessary for adults over 70 years and individuals with low literacy levels.

Mobilizing social support networks to improve cancer screening: the COACH randomized controlled trial study design.

BACKGROUND: Disadvantaged populations face many barriers to cancer care, including limited support in navigating through the complexities of the healthcare system. Family members play an integral role in caring for patients and provide valuable care coordination; however, the effect of family navigators on adherence to cancer screening has not previously been evaluated. Training and evaluating trusted family members and other support persons may improve cancer outcomes for vulnerable patients. METHODS: Guided by principles of community based participatory research (CBPR), "Evaluating Coaches of Older Adults for Cancer Care and Healthy Behaviors (COACH)" is a community-based randomized controlled trial to assess the effectiveness of a trained participant-designated coach (support person or care giver) in navigating cancer-screening for older African American adults, 50-74 years old. Participants are randomly assigned as dyads (participant+coach pair) to receiving either printed educational materials only (PEM--control group) or educational materials plus coach training (COACH--intervention group). We defined a coach as family member, friend, or other lay support person designated by the older adult. The coach training is designed as a one-time, 35- to 40-minute training consisting of: 1) a didactic session that covers the role of the coach, basic facts about colorectal, breast and cervical cancers (including risk factors, signs and symptoms and screening modalities), engaging the healthcare provider in cancer screening, insurance coverage for screening, and related healthcare issues, 2) three video skits addressing misconceptions about and planning for cancer screening, and 3) an interactive role-play session with the trainer to reinforce and practice strategies for encouraging the participant to get screened. The primary study outcome is the difference in the proportion of participants completing at least one of the recommended screenings (for breast, cervix or colorectal cancer) between the control and intervention groups. DISCUSSION: Building on trusted patient contacts to encourage cancer screening, COACH is a highly sustainable intervention in a high-risk population. It has the potential to minimize the effect of mistrust of the medical establishment on screening behaviors by mobilizing participants' existing support networks. If effective, the intervention could have a high impact on health care disparities research across multiple diseases. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01613430 ). Registered June 5, 2012.

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

A genome-wide association study of bronchodilator response in Latinos implicates rare variants.

BACKGROUND: The primary rescue medication to treat acute asthma exacerbation is the short-acting ß2-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). OBJECTIVE: To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. METHODS: We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. RESULTS: We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P < 5 × 10(-8)), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, <5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. CONCLUSION: Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR.

State-of-the-science of patient navigation as a strategy for enhancing minority clinical trial accrual.

BACKGROUND: Patient navigation programs are emerging that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process as well as outcome measures to evaluate program effectiveness. METHODS: A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. RESULTS: The eligible studies reported on the development of programs for patient navigation in cancer clinical trials, including training and implementation among African Americans, American Indians, and Native Hawaiians. A low rate of clinical trial refusal (range, 4%-6%) was reported among patients enrolled in patient navigation programs. However, few studies reported on the efficacy of patient navigation in increasing clinical treatment trial enrollment. CONCLUSIONS: Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients.

Five National Cancer Institute-designated cancer centers' data collection on racial/ethnic minority participation in therapeutic trials: a current view and opportunities for improvement.

BACKGROUND: To ensure that National Institutes of Health-funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI. METHODS: EMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets. RESULTS: Cancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers. CONCLUSIONS: Catchment area definitions and the collection of patient-level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States.

Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation.

MOTIVATION: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging. RESULTS: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. AVAILABILITY AND IMPLEMENTATION: We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Predictors of plasma cell disorders among African American patients: a community practice perspective.

African Americans have two- to three-fold higher incidence of multiple myeloma and MGUS compared to other ethnic groups in the USA. Some physicians often perform diagnostic evaluations for plasma cell disorders (PCD) in African American patients on the basis of hematological abnormalities (thrombocytopenia, leucopenia, etc.) even in the absence of traditional triggers such as anemia, renal impairment, hypercalcemia, hyperglobulinemia, and lytic bone disease. Whether these nontraditional triggers have any significant association with PCD in African American population is not known. In addition, whether this approach could detect more asymptomatic PCD than black population prevalence is questionable. Moreover, the association between traditional triggers and PCD particularly in blacks has not been clearly delineated. Hence, we have carried out a retrospective study in an attempt to answer these questions. Two hundred fifty-four patients were eligible. Multiple myeloma workup based on parameters other than traditional triggers did not detect more asymptomatic PCD than what is expected of black population prevalence (p = 0.19). Of traditional triggers, the finding of only anemia or hyperglobulinemia seemed to be nonspecific in black population (p = 0.17 and 0.85, respectively). However, the presence of serum creatinine >2 mg/dL or corrected serum calcium >10.5 mg/dL or a combination of traditional triggers appeared to be strongly predictive of PCD (odds ratio of 6.9, 4.2, and 3, respectively). The number of trigger variables was positively correlated with the likelihood of PCD (p < 0.001). Light-chain-only PCD, renal disease, and abnormal free light chain ratio seemed to be higher in black patients than their white counterparts.

Examination of race disparities in physical inactivity among adults of similar social context.

OBJECTIVE: The objective of the study was to determine whether race disparities in physical inactivity are present among urban low-income Blacks and Whites living in similar social context. DESIGN: This analysis included Black and White respondents ( > or = 18 years) from the Exploring Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB; N=1350) Study and the National Health Interview Survey (NHIS; N = 67790). Respondents who reported no levels of moderate or vigorous physical activity, during leisure time, over a usual week were considered physically inactive. RESULTS: After controlling for confounders, Blacks had higher adjusted odds of physical inactivity compared to Whites in the national sample (odds ratio [OR] = 1.40; 95% confidence interval [CI] =1.30-1.51). In EHDIC-SWB, Blacks and Whites had a similar odds of physical inactivity (OR = 1.09; 95% CI .86-1.40). CONCLUSION: Social context contributes to our understanding of racial disparities in physical inactivity.

Fast and accurate inference of local ancestry in Latino populations.

MOTIVATION: It is becoming increasingly evident that the analysis of genotype data from recently admixed populations is providing important insights into medical genetics and population history. Such analyses have been used to identify novel disease loci, to understand recombination rate variation and to detect recent selection events. The utility of such studies crucially depends on accurate and unbiased estimation of the ancestry at every genomic locus in recently admixed populations. Although various methods have been proposed and shown to be extremely accurate in two-way admixtures (e.g. African Americans), only a few approaches have been proposed and thoroughly benchmarked on multi-way admixtures (e.g. Latino populations of the Americas). RESULTS: To address these challenges we introduce here methods for local ancestry inference which leverage the structure of linkage disequilibrium in the ancestral population (LAMP-LD), and incorporate the constraint of Mendelian segregation when inferring local ancestry in nuclear family trios (LAMP-HAP). Our algorithms uniquely combine hidden Markov models (HMMs) of haplotype diversity within a novel window-based framework to achieve superior accuracy as compared with published methods. Further, unlike previous methods, the structure of our HMM does not depend on the number of reference haplotypes but on a fixed constant, and it is thereby capable of utilizing large datasets while remaining highly efficient and robust to over-fitting. Through simulations and analysis of real data from 489 nuclear trio families from the mainland US, Puerto Rico and Mexico, we demonstrate that our methods achieve superior accuracy compared with published methods for local ancestry inference in Latinos.

Case-control admixture mapping in Latino populations enriches for known asthma-associated genes.

BACKGROUND: Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. OBJECTIVE: We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. METHODS: We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. RESULTS: Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10(-3) that were significantly enriched for previously identified asthma-associated genes (P= .0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. CONCLUSION: Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.