Biology subjects

Ziv, E.

Publications and source records attributed to Ziv, E..

3 recordsLinked to original sources

bioRxiv2018

Identification of Novel Common Breast Cancer Risk Variants in Latinas at the 6q25 Locus

Background: Breast cancer is a partially heritable trait and over 180 common genetic variants have been associated with breast cancer in genome wide association studies (GWAS). We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25 with the protective minor allele originating from Indigenous American ancestry. Here we report on additional GWAS and replication in Latinas.\n\nMethods: We performed GWAS in 2385 cases and 7342 controls who were either U.S. Latinas or Mexican women. We replicated 2412 cases and 1620 controls of U.S Latina, Mexican, and Colombian women. In addition, we replicated the top novel variants in study of African American and African women and in one study of Chinese women. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model based approach.\n\nResults: We identified 3 SNPs (p=1.9x10-8 - 2.8x10-8) at 6q25 locus not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.75 (0.68-0.83). In a replication in women of Latin American origin, we also observed a consistent effect (OR: 0.88; 95% CI: 0.78-0.99; p=0.037). Since the minor allele was common in East Asians and African American but not European ancestry populations, we replicated in a meta-analysis of those populations and also observed a consistent effect (OR 0.94; 95% CI: 0.91 - 0.97; p=0.013).\n\nConclusion: The effect size of this variant is relatively large compared to other common variants associated with breast cancer and adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

genetics↗

bioRxiv2018

Genetic analysis of Sephardic ancestry in the Iberian Peninsula

The Sephardim are a major Jewish ethnic division whose origins can be traced back to the Iberian Peninsula. We used genome-wide SNP data to investigate the degree of Sephardic admixture in seven populations from the Iberian Peninsula and surrounding regions in the aftermath of their religious persecution starting in the late 14th century. To this end, we used Eastern Mediterranean (from South Italy, Greece and Israel) and North African (Tunisian and Moroccan) populations as proxies for the major ancestral components found in the target populations and carried out unlinked- and linked-marker analyses on the available genetic data. We report evidence of Sephardic ancestry in some of our Iberian samples, as well as in North Italy and Tunisia. We find the Sephardic admixture to be more recent relative to the Berber admixture following an out-of-Iberia geographic dispersal, suggesting Sephardic gene flow from Spain outwards. We also report some of the challenges in assigning Sephardic ancestry to potentially admixed individuals due to the lack of a clear genetic signature.

genomics↗

bioRxiv2017

Creating ethnicity-specific reference intervals for lab tests from EHR data

The results of clinical lab tests are an essential component of medical decision-making. To guide interpretation, test results are returned with reference intervals defined by the range in which 95% of values occur in healthy individuals. Clinical laboratories often set their own reference intervals to accommodate local population and instruments variations. This approach is costly and can be biased. We describe a novel data-driven method for using electronic health record data to extract healthy patients information to define reference intervals. We found that the distributions of many clinical lab tests differ among self-identified racial and ethnic groups (SIREs) in healthy patients. Finally, we derived SIRE-specific reference intervals and provide evidence that these intervals have clinical prognostic value. Specifically, we show that for two lab tests, serum creatinine level and hemoglobin A1C, SIRE-specific reference intervals are more predictive for need for dialysis and development type 2 diabetes than existing reference intervals.\n\nOne Sentence SummaryA novel method for defining population-specific reference intervals of common clinical laboratory tests from electronical health records has better prognostic value than existing reference intervals.

bioinformatics↗