Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

Freedman, Matthew L.; Haiman, Christopher A.; Patterson, Nick; McDonald, Gavin J.; Tandon, Arti; Waliszewska, Alicja; Penney, Kathryn L.; Steen, Robert; Ardlie, Kristin; John, Esther M.; Oakley-Girvan, Ingrid; Whittemore, Alice S.; Cooney, Kathleen A.; Ingles, Sue A.; Altshuler, David; Henderson, Brian E.; Reich, David

doi:10.1073/pnas.0605832103

Cited by 579 publications

(515 citation statements)

References 23 publications

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“…[27][28][29][30] Recent studies, however, have shown considerable fractions of Amerindian ancestral component in many African-American individuals. 1,13 Using STRUCTURE, 31,32 we estimated the genetic contribution of African, European and Amerindian/East Asian populations to the 2114 African-Americans to be 0.725, 0.245 and 0.029, respectively (K ¼ 3).…”

Section: Lacs Distributions Facilitated Inference Of African-americanmentioning

confidence: 99%

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

Jin

Zhou

et al. 2013

Eur J Hum Genet

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The ancestral chromosomal segments in admixed genomes are of significant importance for both population history inference and admixture mapping, because they essentially provide the basic information for tracking genetic events. However, the distributions of the lengths of ancestral chromosomal segments (LACS) under some admixture models remain poorly understood. Here we introduced a theoretical framework on the distribution of LACS in two representative admixture models, that is, hybrid isolation (HI) model and gradual admixture (GA) model. Although the distribution of LACS in the GA model differs from that in the HI model, we demonstrated that the mean LACS in the HI model is approximately half of that in the GA model if both admixture proportion and admixture time in the two models are identical. We showed that the theoretical framework greatly facilitated the inference and understanding of population admixture history by analyzing African-American and Mexican empirical data. In addition, we found the peak of association signatures in the HI model was much narrower and sharper than that in the GA model, indicating that the identification of putative causal allele in the HI model is more efficient than that in the GA model. Thus admixture mapping with case-only data would be a reasonable and economical choice in the HI model due to the weak background noise. However, according to our previous studies, many populations are likely to be gradually admixed and have pretty high background linkage disequilibrium. Therefore, we suggest using a case-control approach rather than a case-only approach to conduct admixture mapping to retain the statistics power in recently admixed populations.

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Section: Lacs Distributions Facilitated Inference Of African-americanmentioning

confidence: 99%

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

Jin

Zhou

et al. 2013

Eur J Hum Genet

View full text Add to dashboard Cite

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“…http://doc.rero.ch [27][28][29][30][31]. However, multiple studies have identified genetic variants associated with lighter and darker skin pigmentation in humans [32][33][34], a trait that might be differentially selected in regions with low and high ultraviolet radiation (UVR), owing to known associations between skin pigmentation and vitamin D synthesis and protection from UVR [34,35].…”

Section: Box 2 Relationship Between Admixture and Association Mappingmentioning

confidence: 99%

Admixture as the basis for genetic mapping

Buerkle

Lexer

2008

Trends in Ecology & Evolution

162

204

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“…Only when specific associations are validated in multiple large cohorts will the scientific community have confidence in the purported findings from such studies. Although it is currently unknown whether or not 8q24 is related to inflammatory pathways, one very recent example of a success story stems from a set of independent studies that implicated this chromosome region in prostate cancer occurring in both families and in sporadic cases 130,131 . …”

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Inflammation in prostate carcinogenesis

et al. 2007

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About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease. NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2013 January 23. $watermark-text $watermark-text $watermark-textProstate cancer is the most common non-cutaneous malignant neoplasm in men in Western countries, responsible for the deaths of approximately 30,000 men per year in the United States 1 . The number of afflicted men is increasing rapidly as the population of males over the age of 50 grows worldwide. Therefore, finding strategies for the prevention of prostate cancer is a crucial medical challenge. As men in South East Asian countries have a low incidence of prostate cancer that increases rapidly after immigration to the West, this disease is not an intrinsic feature of ageing. The pathogenesis of prostate cancer reflects both hereditary and environmental components. What are the environmental factors and genetic variations that have produced such an epidemic of prostate cancer? Approximately 20% of all human cancers in adults result from chronic inflammatory states and/or chronic inflammation 2-4 (BOX 1), which are triggered by infectious agents or exposure to other environmental factors, or by a combination thereof. There is also emerging evidence that inflammation is crucial for the aetiology of prostate cancer. This evidence stems from epidemiological, histopathological and molecular pathological studies. The objective of this Review is to take a multidisciplinary approach to present and analyse such studies. Because several reviews related to these topics have been published [5][6][7] , here we will focus on new findings and ideas with the purpose of sparking innovative areas of investigation that might ultimately lead to the prevention of prostate cancer. Enigmas in the aetiology of prostate cancerAs in other cancers, prostate cancer develops through the accumulation of somatic genetic and epigenetic changes, resulting in the inactivation of tumour-suppressor genes and caretaker genes, and the activation of oncogenes 8,9 (TABLE 1). There is also evidence for an underlying genetic instability that might facilitate tumour progression 10,11 . Although these genetic and epigenetic changes are crucial for our understanding of 'how' prostate cancer arises, another key remaining question is 'why'...

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Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

Cited by 579 publications

References 23 publications

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

Admixture as the basis for genetic mapping

Inflammation in prostate carcinogenesis

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