Genetics Research
rs1926657
Gene: ABCC4 — ATP Binding Cassette Subfamily C Member 4 (PEL Blood Group)
Chr 13:95222702
13q32.1
Intron Variant
Population Frequencies12
African
T 0.31049C 0.68951TT 0.100039TC/CT 0.420904CC 0.479057pop=55,818
African American
T 0.30933C 0.69067TT 0.099064TC/CT 0.420541CC 0.480395pop=53,864
African Others
T 0.3424C 0.6576TT 0.126919TC/CT 0.430911CC 0.44217pop=1,954
Asian
T 0.33699C 0.66301TT 0.118394TC/CT 0.437202CC 0.444404pop=16,386
East Asian
T 0.33958C 0.66042TT 0.116422TC/CT 0.44631CC 0.437268pop=12,386
European
T 0.166578C 0.833422TT 0.028711TC/CT 0.275735CC 0.695554pop=501,974
Latin American 1
T 0.2438C 0.7562TT 0.05827TC/CT 0.371101CC 0.57063pop=6,796
Latin American 2
T 0.23769C 0.76231TT 0.055366TC/CT 0.364646CC 0.579989pop=14,052
Other
T 0.24242C 0.75758TT 0.063337TC/CT 0.358175CC 0.578488pop=22,704
Other Asian
T 0.329C 0.671TT 0.1245TC/CT 0.409CC 0.4665pop=4,000
South Asian
T 0.3048C 0.6952TT 0.098483TC/CT 0.412602CC 0.488915pop=8,570
Studies16
Unread Studies16 ▼
1
Breast cancer development and progression involve both germline and somatic mutations. High‐throughput genotyping and next‐generation sequencing technologies …
2
Genome-wide-association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. Most …
3
Over the last twenty-five years, researchers have identified several dozen genetic polymorphisms associated with breast cancer susceptibility. While many of these loci are now considered well-established risk factors for the disease, previous attempts to replicate variant-disease associations in African Americans or to identify subtype-specific risk variants have been imprecise and inconsistent. I examined the association between breast cancer subtypes and previously established candidate gene and genome-wide association study hits among white and African American women in the Carolina Breast Cancer Study. Maximum likelihood and Bayesian methods were used to estimate race and subtype-specific odds ratios (ORs) for each of 83 candidate single nucleotide polymorphisms (SNPs). Selected SNPs included several previous GWAS hits (n=22), near-GWAS hits (n=19), otherwise well-established risk loci (n=5), or SNPs in the same gene as another selected variant (n=37). Subtypes were defined using 5 immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2) and cytokeratin (CK) 5/6. Eighteen GWAS-identified SNPs successfully replicated in whites and ten GWAS-identified SNPs successfully replicated in African Americans. SNPs in FGFR2 and TNRC9/TOX3 were strongly associated with breast cancer in both races. Additionally, SNPs in MRPS30, MAP3K1, CDKN2A/B, ZM1Z1, LSP1, H19, and TP53 were associated with breast cancer in whites and SNPs in TLR1, ESR1, and H19 were associated with breast cancer in African Americans. Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like disease (ER-, PR-, HER2-, HER1 or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), and HER2+/ER-, but not basal-like disease. There were also subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1. These analyses provide precise, well-informed race and subtype-stratified ORs for several key breast cancer-related SNPs. These results also demonstrate the utility of Bayesian methods in genetic epidemiology and provide evidence of subtype-specific etiologies. This work may help to identify specific causal variants, locate targets for research on directed therapies, and identify high-risk individuals.
4
Balancing selection can maintain genetic variation in a population over long evolutionary time periods. Identifying genomic loci under this type of selection not only elucidates selective pressures and adaptations but can also help interpret common genetic variation contributing to disease. Summary statistics which capture signatures in the site frequency spectrum are frequently used to scan the genome to detect loci showing evidence of balancing selection. However, these approaches have limited power because they rely on imprecise signatures such as a general excess of heterozygosity or number of genetic variants. A second class of statistics, based on likelihoods, have higher power but are often computationally prohibitive. In addition, a majority of methods in both classes require a high-quality sequenced outgroup, which is unavailable for many species of interest. Therefore, there is a need for a well-powered and widely-applicable statistical approach to detect balancing selection. Theory suggests that long-term balancing selection will result in a genealogy with very long internal branches. In this thesis, I show that this leads to a precise signature: an excess of genetic variants at near identical allele frequencies to one another. We have developed novel summary statistics to detect this signature of balancing selection, termed the β statistics. Using simulations, we show that these statistics are not only computationally light but also have high power even if an outgroup is unavailable. We have derived the variance of these statistics, allowing proper comparison of β values across sample sizes, mutation rates, and allele frequencies variables not fully accounted for by many previous methods. We scanned the 1000 Genomes Project data with β to find balanced loci in humans. Here, I report multiple balanced haplotypes that are strongly linked to both association signals for complex traits and regulatory variants, indicating balancing selection may be affecting complex trait architecture. Due to their high power and wide applicability, the β statistics enable evolutionary biologists to detect targets of balancing selection in a range of species and with a degree of specificity previously unattainable.
5
Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate–binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals.
6
Purpose Genome-wide-association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. Most of these studies were conducted primarily in postmenopausal breast cancer patients. Therefore, we set out to assess whether or not these breast cancer variants are also associated with an elevated risk of breast cancer in young premenopausal patients. Methods In 451 women of European ancestry who had prospectively enrolled in a longitudinal cohort study for women diagnosed with breast cancer at or under age 40, we genotyped 44 SNPs that were previously associated with breast cancer risk. A control group was comprised of 1142 postmenopausal healthy women from the Nurses’ Health Study (NHS). We assessed if the frequencies of the adequately genotyped SNPs differed significantly (p≤0.05) between the cohort of young breast cancer patients and postmenopausal controls, and then we corrected for multiple testing. Results Genotyping of the controls or cases was inadequate for comparisons between the groups for seven of the 44 SNPs. 9 of the remaining 37 were associated with breast cancer risk in young women with a p-value <0.05: rs10510102, rs1219648, rs13387042, rs1876206, rs2936870, rs2981579, rs3734805, rs3803662 and rs4973768. The directions of these associations were consistent with those in postmenopausal women. However, after correction for multiple testing (Benjamini Hochberg) none of the results remained statistically significant. Conclusion After correction for multiple testing, none of the alleles for postmenopausal breast cancer were clearly associated with risk of premenopausal breast cancer in this relatively small study.
7
Breast Cancer is the most common cancer among women with several genes involved in disease susceptibility. As majority of genome-wide significant variants fall outside the coding …
8
The notion of disease-associated single-nucleotide polymorphisms (da-SNP), as determined in genome-wide association studies (GWAS), is relevant for many complex pathologies, including cancers. It appeared that da-SNPs are not only markers of causal genetic variation but may contribute to the disease development through an influence on gene expression levels. We argue that understanding this possible functional role of da-SNPs requires to consider their embedding in the tridimensional (3D) multi-scale organization of the human genome. We then focus on the potential impact of da-SNPs on chromatin loops and recently observed topologically associating domains (TADs). We show that for some diseases and cancer types, da-SNPs are over-represented in the borders of these topological domains, in a way that cannot be explained by an increased exon density. This analysis of the distribution of da-SNPs within the 3D genome organization suggests candidate loci for further experimental investigation of the mechanisms underlying genetic susceptibility to diseases, in particular cancer.
9
The aim of this study is to examine a large dataset of single nucleotide polymorphism known to be associated with prostate cancer from previous genome-wide association studies and …
10
Genome-wide association studies and epigenome-wide association studies go together in cancer control
Completion of the human genome a decade ago laid the foundation for: using genetic information in assessing risk to identify individuals and populations that are likely to develop …
11
… In our study, rs1926657 and rs6556756 were significantly identified to be related to BC risk while rs1978503 and rs2075555 were not. These may be due to the different genetic …
12
An integrative genomics approach for associating GWAS information with triple-negative breast cancer
Genome-wide association studies (GWAS) have identified genetic variants associated with an increased risk of developing breast cancer. However, the association of genetic variants …
13
… In our study, rs1926657 and rs6556756 were significantly identified to be related to BC risk while rs1978503 and rs2075555 were not. These may be due to the different genetic …
14
Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing …
15
Genome-wide association studies (GWAS) have successfully identified genetic variants associated with risk for breast cancer. However, the molecular mechanisms through which the …
16
Breast cancer is a heterogeneous, polygenic disease and is influenced by genetic, environmental and life-style factors. Many single nucleotide polymorphisms (SNPs) associated with …
Curated Studies0 ▼
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