Estimating the contribution of genetic variants to difference in incidence of disease between population groups

Moonesinghe, Ramal; Ioannidis, John P. A.; Flanders, W. Dana; Yang, Quanhe; Truman, Benedict I.; Khoury, Muin J.

doi:10.1038/ejhg.2012.15

Cited by 22 publications

(19 citation statements)

References 19 publications

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“…The inconsistent findings for HBV- and HCV-related HCC suggest that whether SNPs in the MICA and DEPDC5 loci affect the susceptibility to HCC is subject to race/ethnicity-specific differences. Undoubtedly, the same variability also applies to all the other HCC-related SNPs, which could be explained by gene-gene and gene-environment interactions contributing to the inconsistent findings in different racial or ethnic groups that have been studied[95]. …”

Section: Snpsmentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

137

108

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

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Section: Snpsmentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

137

108

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“…This is consistent with general definitions of the term used in the population genetics literature [1] . In this light, although it has been shown that a greater proportion of global genetic variation can be attributed to differences among individuals within populations rather than to differences between individuals from separate populations [2][3][4][5][6] , stratification or genetic differentiation between individuals from different populations is not negligible on a global scale and has important implications for gene mapping studies, public health campaigns, and clinical studies and practices [7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

“…In addition, there are many phenotypes that have emerged in different populations due to different genetic variants or sets of causative variants arising in those populations (i.e. the genetic causes of these phenotypes manifest locus or allelic heterogeneity) [8] . Thus, it might be the case that two individuals, who present with the same condition but have different ancestral backgrounds, have different genetic bases for that condition.…”

Section: Introductionmentioning

confidence: 99%

Admixture and Clinical Phenotypic Variation

Goetz¹,

Uribe-Bruce²,

Quarless³

et al. 2014

Hum Hered

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All human populations exhibit some level of genetic differentiation. This differentiation, or population stratification, has many interacting sources, including historical migrations, population isolation over time, genetic drift, and selection and adaptation. If differentiated populations remained isolated from each other over a long period of time such that there is no mating of individuals between those populations, then some level of global consanguinity within those populations will lead to the formation of gene pools that will become more and more distinct over time. Global genetic differentiation of this sort can lead to overt phenotypic differences between populations if phenotypically relevant variants either arise uniquely within those populations or begin to exhibit frequency differences across the populations. This can occur at the single variant level for monogenic phenotypes or at the level of aggregate variant frequency differences across the many loci that contribute to a phenotype with a multifactorial or polygenic basis. However, if individuals begin to interbreed (or ‘admix') from populations with different frequencies of phenotypically relevant genetic variants, then these admixed individuals will exhibit the phenotype to varying degrees. The level of phenotypic expression will depend on the degree to which the admixed individuals have inherited causative variants that have descended from the ancestral population in which those variants were present (or, more likely, simply more frequent). We review studies that consider the association between the degree of admixture (or ancestry) and phenotypes of clinical relevance. We find a great deal of literature-based evidence for associations between the degree of admixture and phenotypic variation for a number of admixed populations and phenotypes, although not all this evidence is confirmatory. We also consider the implications of such associations for gene-mapping initiatives as well as general clinical epidemiology studies and medical practice. We end with some thoughts on the future of studies exploring phenotypic differences among admixed individuals as well as individuals with different ancestral backgrounds.

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“…; Moonesinghe et al. ). Non‐replication can be attributed to an uneven distribution of alleles within subpopulations or population substructure (Falush, Stephens, and Pritchard ).…”

Section: The Uncertainty Of Race In the Post‐genomic Agementioning

confidence: 97%

“…Of most relevance to human variation and GWAS is the problem of non-replication of significant associations across human groups. With non-replication, genetic variants that confer disease risk within one population do not hold the same significant risk in other populations (Huang et al 2016;Marigorta et al 2011;Moonesinghe et al 2012). Non-replication can be attributed to an uneven distribution of alleles within subpopulations or population substructure (Falush, Stephens, and Pritchard 2003).…”

Section: The Uncertainty Of Race In Thementioning

confidence: 99%

Race, Rare Genetic Variants, and the Science of Human Difference in the Post‐Genomic Age

Torres

2019

Transforming Anthropology

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Understanding of human genetic variation has grown significantly in the twenty‐first century but has not been adequately incorporated into anti‐racist anthropological perspectives. Research into the underlying structure of human disease suggests that common diseases may be caused by rare genetic variants. These variants tend to be specific to populations that are oftentimes racially defined. Consequently, genetic studies that seek to identify disease‐causing rare variants rely upon racialized frameworks. Despite social scientific perspectives that endorse a nonbiological basis to race, within biomedicine, biological uses of race remain entrenched due to their utility for identifying the causes of the disease. Anthropologists must be responsive to these utilizations of race or risk irrelevance in shaping how researchers understand and use human variation. Through critique and careful incorporation of new knowledge about the nature of human genetic variation into anthropological perspectives, anthropologists can continue to make meaningful contributions to understanding the relationship between biology and race.

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Estimating the contribution of genetic variants to difference in incidence of disease between population groups

Cited by 22 publications

References 19 publications

Genetic alterations in hepatocellular carcinoma: An update

Genetic alterations in hepatocellular carcinoma: An update

Admixture and Clinical Phenotypic Variation

Race, Rare Genetic Variants, and the Science of Human Difference in the Post‐Genomic Age

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