African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in .

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

The Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO): Design and Baseline Characteristics for a Birth Cohort Study of Early-life Viral Respiratory Illnesses and Airway Dysfunction in Puerto Rican Children.

Epidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if early-life RIs induce alterations in airway function, immune responses, or other human biology that contribute to the development of asthma. Puerto Rican children experience a disproportionate burden of early-life RIs and asthma, making them an important population for investigating this complex interplay.

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.

Race/Ethnicity and Clinical Prediction Algorithms for Childhood Asthma.

In 1985, the United States Department of Health and Human Services released the Report of the Secretary's Task Force on Black & Minority Health. The landmark report showed that persistent health disparities accounted for excess mortality among ethnic and racial minoritized groups. Since this report was published, many efforts have been made to improve clinical outcomes between White and non-White populations.

Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

We explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments.

Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies.

Background: Asthma disproportionately affects minority populations and is associated with psychosocial stress such as racial/ethnic discrimination. We aimed to examine the association of perceived discrimination with asthma and poor asthma control in African American and Latino youth.

Methods: We included African American (n = 954), Mexican American (n = 1,086), other Latino (n = 522), and Puerto Rican Islander (n = 1,025) youth aged 8 to 21 years from the Genes-Environments and Admixture in Latino Americans study and the Study of African Americans, Asthma, Genes, and Environments.

Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.

The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.

Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation.

Differing effects of metformin on glycemic control by race-ethnicity.

Context: Metformin is considered first-line treatment for type 2 diabetes mellitus. However, little is known about its effects in African American individuals.

Objective: The objective of the study was to assess whether metformin's effect on glycemic control differs by race-ethnicity Design: Electronic health records were used to identify adults who had a diagnosis of diabetes, two or more fills of metformin, and two or more glycated hemoglobin (HbA1c) measurements.

GeneOnEarth: fitting genetic PC plots on the globe.

Principal component (PC) plots have become widely used to summarize genetic variation of individuals in a sample. The similarity between genetic distance in PC plots and geographical distance has shown to be quite impressive. However, in most situations, individual ancestral origins are not precisely known or they are heterogeneously distributed; hence, they are hardly linked to a geographical area.

Role of interactions in pharmacogenetic studies: leukotrienes in asthma.

Researchers have identified thousands of loci involved in complex traits and drug response. However, in most cases they only explain a small proportion of the heritability of the trait. Among different strategies conducted to identify this 'missing heritability', here we illustrate the importance of complex gene-environment interactions using findings regarding the role of leukotrienes on the bronchodilator response to albuterol in Latino asthmatics.

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.

Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the incidence of ALL varies by ethnicity. Although accumulating evidence indicates inherited predisposition to ALL, the genetic basis of ALL susceptibility in diverse ancestry has not been comprehensively examined.

Methods: We performed a multiethnic genome-wide association study in 1605 children with ALL and 6661 control subjects after adjusting for population structure, with validation in three replication series of 845 case subjects and 4316 control subjects.

Genetic ancestry and its association with asthma exacerbations among African American subjects with asthma.

Background: There are large and persisting disparities in severe asthma exacerbations by race-ethnicity, and African American subjects are among those at greatest risk. It is unclear whether this increased risk solely represents differences in environmental exposures and health care or whether there is a predisposing genetic component.

Objective: We sought to assess the relationship between genetic ancestry and severe exacerbations among African American subjects with asthma.

Melanesian blond hair is caused by an amino acid change in TYRP1.

Naturally blond hair is rare in humans and found almost exclusively in Europe and Oceania. Here, we identify an arginine-to-cysteine change at a highly conserved residue in tyrosinase-related protein 1 (TYRP1) as a major determinant of blond hair in Solomon Islanders. This missense mutation is predicted to affect catalytic activity of TYRP1 and causes blond hair through a recessive mode of inheritance.

Heterogeneity in genetic admixture across different regions of Argentina.

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates.

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.

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.

Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas.

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays.

Ethnic variability in persistent asthma after in utero tobacco exposure.

Background: The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.

Objective: To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.

Patients And Methods: There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview.

Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM).