Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer

Henrion, Marc; Frampton, Matthew; Scélo, Ghislaine; Purdue, Mark P.; Ye, Yuanqing; Broderick, Peter; Ritchie, A. W. S.; Kaplan, Richard; Meade, Angela; McKay, James; Johansson, Mattias; Lathrop, Mark; Larkin, James; Rothman, Nathaniel; Wang, Zhaoming; Chow, Wong Ho; Stevens, Victoria L.; Diver, W. Ryan; Gapstur, Susan M.; Albanês, Demetrius; Virtamo, Jarmo; Wu, Xifeng; Brennan, Paul; Chanock, Stephen J.; Eisen, Timothy; Houlston, Richard S.

doi:10.1093/hmg/dds489

Cited by 55 publications

(45 citation statements)

References 25 publications

(35 reference statements)

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“…Logistic regression is used throughout to test for association between SNPs and disease. Results for the fifth variant, located on 2q22.3, are nonsignificant but the effect is in the same direction as originally reported 7 (P ¼ 0.51, odds ratio (OR) ¼ 1.10).…”

Section: Gwas Data and Imputation In Icelandic Samplessupporting

confidence: 78%

“…Rare, high-penetrance mutations accounting for syndromic RCC have been found in several genes, including VHL, MET, FLCN and FH 4 . Genome-wide association studies (GWAS) have reported five sporadic RCC susceptibility loci [5][6][7] . However, in combination, these risk variants account for only a small fraction of the approximately twofold greater than the average risk of RCC in first-degree relatives of RCC patients 1,2 .…”

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confidence: 99%

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A common variant at 8q24.21 is associated with renal cell cancer

et al. 2013

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Section: Gwas Data and Imputation In Icelandic Samplessupporting

confidence: 78%

mentioning

confidence: 99%

A common variant at 8q24.21 is associated with renal cell cancer

et al. 2013

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“…The SNP is located in an enhancer regulatory feature (Rosenbloom et al 2011;Dunham et al 2012) located between genes PELI1 and VPS54, in the same putatively selected region as that of genes EHBP1 and OTX1 (see above). Finally, there is a highly C-scoring SNP (rs731108) that is associated with renal cell carcinoma (Henrion et al 2013). This SNP is also located in an enhancer regulatory feature (Rosenbloom et al 2011;Dunham et al 2012), in an intron of ZEB2.…”

Section: Selection In Ancestral Modern Humansmentioning

confidence: 99%

Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation

Racimo

2015

Genetics

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A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality and finding which model is most compatible with the data. A previous method based on a cross-population composite likelihood ratio (XP-CLR) uses an outgroup population to detect departures from neutrality that could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method -called "3-population composite likelihood ratio" (3P-CLR) -outperforms XP-CLR when testing for selection that occurred before two populations split from each other and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Yoruba and Eurasians, but after their split from Neanderthals, and that could have led to the spread of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans, and the ancestors of both populations, after their split from Yoruba. In both cases, we are able to confirm a number of regions identified by previous methods and find several new candidates for selection in recent and ancient times. For some of these, we also find suggestive functional mutations that may have driven the selective events.

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“…Recent genome-wide association studies (GWAS) conducted among study populations of European ancestry have identified four susceptibility loci for RCC (6–8). The variant rs7579899 maps to EPAS1 on 2p21, which encodes HIF-2α, a critical factor in HIF/VHL-mediated development of ccRCC (5).…”

Section: Introductionmentioning

confidence: 99%

“…The variant rs7579899 maps to EPAS1 on 2p21, which encodes HIF-2α, a critical factor in HIF/VHL-mediated development of ccRCC (5). The variants rs7105934, on 11q13.3, and rs12105918, mapping to ZEB2 on 2q22.3, are also suspected to influence RCC risk in a HIF-dependent manner (6, 8, 9). The biologic basis for the association with rs718314 (mapping to ITPR2 on 12p11.23) is unclear, although ITPR2 was associated with waist-to-hip ratio in an earlier GWAS (10); the latter is interesting because an elevated BMI is an established risk factor for RCC in all populations studied (2).…”

Section: Introductionmentioning

confidence: 99%

A Genome-Wide Association Study of Renal Cell Carcinoma among African Americans

Purdue

Wang

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Genome-wide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AAs), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNPs) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases, 543 controls). The 12p11.23 variant rs10771279, located 77kb from the European-ancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P=1.2 × 10−7) but did not replicate (P=0.99). Consistent with European-ancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [odds ratio (OR)=0.76, 95% confidence interval (CI)=0.64–0.91; P=0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07 respectively among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR=0.56; P=7.4 × 10−7) and absent for cases of other or unknown histology (OR=1.02; P=0.86). Analyses of rs7105934 by subtype among European-ancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92 respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to ccRCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed.

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Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer

Cited by 55 publications

References 25 publications

A common variant at 8q24.21 is associated with renal cell cancer

A common variant at 8q24.21 is associated with renal cell cancer

Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation

A Genome-Wide Association Study of Renal Cell Carcinoma among African Americans

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