APOL1 Nephropathy: A Population Genetics and Evolutionary Medicine Detective Story

Kruzel-Davila, Etty; Wasser, Walter G.; Skorecki, Karl

doi:10.1016/j.semnephrol.2017.07.002

Cited by 39 publications

(36 citation statements)

References 163 publications

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“…Angiogenesis and inflammatory response terms are highly biologically relevant to health disparities that affect AAs, as AAs are more susceptible to CVD and other chronic inflammatory disease. In particular, APOL1, PTGIS and PLAT expression, which we show to be associated with percentage of WAA, have been shown to increase CVD risk and renal disease in AAs (Kruzel-Davila et al, 2017;Nagareddy & Smyth, 2013;Notarangelo, Bontardelli, & Merlini, 2013). Other interesting associations include ALDH1A1, which is involved in alcohol and aldehyde metabolism disorders and cancer (Scott & Taylor, 2007;Vasiliou & Pappa, 2000;Y.…”

Section: Discussionmentioning

confidence: 66%

“…AAs have a higher risk of cardiovascular events and negative outcomes from adverse antiplatelet drug response (Cresci et al, 2014). They have higher incidences of death and disability from cardiovascular diseases (CVDs), thrombosis, renal dysfunction and pathologies, diabetes, cancers, alcoholism and other metabolic disorders (Boulter et al, 2015;De, Alarcon, et al, 2018;Kruzel-Davila, Wasser, & Skorecki, 2017; Y. C. Li, 2013; C. T. Liu et al, 2011;Mishra et al, 2013;Sarkissyan et al, 2014;Scott & Taylor, 2007;Sivaskandarajah et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Uncovering the role of admixture in disease and drug response: Association of hepatocyte gene expression and DNA methylation with African Ancestry in African Americans

Park¹,

De²,

et al. 2018

Preprint

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BackgroundAfrican Americans (AAs) are an admixed population with portions of their genome derived from West Africans and Europeans. In AAs, the proportion of West African ancestry (WAA) can vary widely and may explain the genetic drivers of disease, specifically those that disproportionately affect this understudied population. To examine the relationship between the proportion of WAA and gene expression, we used high dimensional data obtained from AA primary hepatocytes, a tissue important in disease and drug response.MethodsRNA sequencing (Illumina HiSeq Platform) was conducted on 60 AA-derived primary hepatocytes, with methylation profiling (Illumina MethylationEPIC BeadChip) of 44 overlapping samples. WAA for each sample was calculated using fastSTRUCTURE and correlated to both gene expression and DNA methylation. The GTEx consortium (n = 15) was used for replication and a second cohort (n = 206) was using used for validation using differential gene expression between AAs and European-Americans.ResultsWe identified 131 genes associated with WAA (FDR< 0.1), of which 28 gene expression traits were replicated (FDR<0.1) and enriched in angiogenesis and inflammatory pathways (FDR<0.1). These 28 replicated gene expression traits represented 257 GWAS catalog phenotypes. Among the PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p < 0.05) with replication of CYP2C19 and VDR in GTEx. Association of DNA methylation with WAA identified 1037 differentially methylated regions (FDR<0.05), with hypomethylated genes enriched in drug response pathways. Overlapping of differentially methylated regions with the 131 significantly correlated gene expression traits identified 5 genes with concordant directions of effect: COL26A1, HIC1, MKNK2, RNF135, SNAI1 and TRIM39.ConclusionsWe conclude that WAA contributes to variability in hepatic gene expression and DNA methylation with identified genes indicative of diseases disproportionately affecting AAs. Specifically, WAA-associated genes were linked to previously identified loci in cardiovascular disease (PTGIS, PLAT), renal disease (APOL1) and drug response (CYP2C19).

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Uncovering the role of admixture in disease and drug response: Association of hepatocyte gene expression and DNA methylation with African Ancestry in African Americans

Park¹,

De²,

et al. 2018

Preprint

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“…Genetics of human populations contribute to the propensity and severity of diseases 37,39,41,41,45,[60][61][62][63][64][65] . Sometimes the contribution is straightforward; a single allele variation found in Ashkenazi Jews, causes the vast majority of Tay-Sachs disease 66 .…”

Section: Discussionmentioning

confidence: 99%

Differential expression of COVID-19-related genes in European Americans and African Americans

Singh

Wurtele

2020

Preprint

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The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.

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“…We found that among African Amer-ican patients with ESRD due to LN, the level of improvement in all-cause mortality over time was similar to-and not better thanthe level of improvement over time among white patients, suggesting that the mortality disparity did not change. Multiple factors have been proposed to contribute to worse outcomes among African American patients with LN-associated ESRD, including differences in socioeconomic status (12) and genetic predisposition to renal disease progression, such as the APOL1 mutation (23,24). Historically, African American patients generally had a lower rate of renal transplantation (particularly preemptive renal transplantation) than white patients with ESRD, although this may be improving in recent years (25).…”

Section: Discussionmentioning

confidence: 99%

All‐Cause and Cause‐Specific Mortality Trends of End‐Stage Renal Disease Due to Lupus Nephritis From 1995 to 2014

Jorge

Wallace

Zhang

et al. 2019

Arthritis & Rheumatology

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APOL1 Nephropathy: A Population Genetics and Evolutionary Medicine Detective Story

Cited by 39 publications

References 163 publications

Uncovering the role of admixture in disease and drug response: Association of hepatocyte gene expression and DNA methylation with African Ancestry in African Americans

Uncovering the role of admixture in disease and drug response: Association of hepatocyte gene expression and DNA methylation with African Ancestry in African Americans

Differential expression of COVID-19-related genes in European Americans and African Americans

All‐Cause and Cause‐Specific Mortality Trends of End‐Stage Renal Disease Due to Lupus Nephritis From 1995 to 2014

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