Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
11,535
result(s) for
"Ethnic Groups - genetics"
Sort by:
Multi-ethnic genome-wide association study for atrial fibrillation
Atrial fibrillation (AF) affects more than 33 million individuals worldwide
1
and has a complex heritability
2
. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.
Journal Article
Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage
The International Stem Cell Initiative compares 125 ethnically diverse human embryonic stem cell lines at early and late passage. Data on karotype, single-nucleotide polymorphisms and methylation shed light on how the cells adapt to long-term culture.
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells,
ID1
,
BCL2L1 and HM13
, occurred in >20% of the lines. Of these genes,
BCL2L1
is a strong candidate for driving culture adaptation of ES cells.
Journal Article
Gut microbiota diversity across ethnicities in the United States
Composed of hundreds of microbial species, the composition of the human gut microbiota can vary with chronic diseases underlying health disparities that disproportionally affect ethnic minorities. However, the influence of ethnicity on the gut microbiota remains largely unexplored and lacks reproducible generalizations across studies. By distilling associations between ethnicity and differences in two US-based 16S gut microbiota data sets including 1,673 individuals, we report 12 microbial genera and families that reproducibly vary by ethnicity. Interestingly, a majority of these microbial taxa, including the most heritable bacterial family, Christensenellaceae, overlap with genetically associated taxa and form co-occurring clusters linked by similar fermentative and methanogenic metabolic processes. These results demonstrate recurrent associations between specific taxa in the gut microbiota and ethnicity, providing hypotheses for examining specific members of the gut microbiota as mediators of health disparities.
Journal Article
Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects’ alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in
ALDH2
and alcohol drinker status (odd ratio (OR)=0.40,
P
=2.28 × 10
−72
) in East Asians, and also an effect on drinks/week (beta=−0.17,
P
=5.42 × 10
−4
) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in
ADH1B
and both alcohol consumption phenotypes (OR=0.79,
P
=2.47 × 10
−20
for drinker status and beta=−0.19,
P
=1.91 × 10
−35
for drinks/week), which replicated in Hispanic/Latinos (OR=0.72,
P
=4.35 × 10
−7
and beta=−0.21,
P
=2.58 × 10
−6
, respectively). Although prior studies reported effects of
ADH1B
and
ALDH2
on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the
KLB
and
GCKR
loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=−0.04,
P
=3.41 × 10
−10
for drinks/week and OR=0.96,
P
=4.08 × 10
−5
for drinker status), and rs4665985 (beta=0.04,
P
=2.26 × 10
−8
for drinks/week and OR=1.04,
P
=5 × 10
−4
for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating
AUTS2
,
SGOL1
and
SERPINC1
genes in alcohol consumption traits in non-Hispanic whites.
Journal Article
Genetic Evidence for High-Altitude Adaptation in Tibet
Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.
Journal Article
Next-generation characterization of the Cancer Cell Line Encyclopedia
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR–Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.
The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.
Journal Article
Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens
Spinal muscular atrophy (SMA) is a leading inherited cause of infant death with a reported incidence of ∼1 in 10 000 live births and is second to cystic fibrosis as a common, life-shortening autosomal recessive disorder. The American College of Medical Genetics has recommended population carrier screening for SMA, regardless of race or ethnicity, to facilitate informed reproductive options, although other organizations have cited the need for additional large-scale studies before widespread implementation. We report our data from carrier testing (
n
=72 453) and prenatal diagnosis (
n
=121) for this condition. Our analysis of large-scale population carrier screening data (
n
=68 471) demonstrates the technical feasibility of high throughput testing and provides mutation carrier and allele frequencies at a level of accuracy afforded by large data sets. In our United States pan-ethnic population, the calculated
a priori
carrier frequency of SMA is 1/54 with a detection rate of 91.2%, and the pan-ethnic disease incidence is calculated to be 1/11 000. Carrier frequency and detection rates provided for six major ethnic groups in the United States range from 1/47 and 94.8% in the Caucasian population to 1/72 and 70.5% in the African American population, respectively. This collective experience can be utilized to facilitate accurate pre- and post-test counseling in the settings of carrier screening and prenatal diagnosis for SMA.
Journal Article
Genomic Insights into the Ancestry and Demographic History of South America
South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical genetic studies in the region.
Journal Article