Genome-wide polygenic score to predict chronic kidney disease across ancestries

Khan, Atlas; Turchin, Michael C.; Patki, Amit; Srinivasasainagendra, Vinodh; Shang, Ning; Nadukuru, Rajiv; Jones, Alana; Małolepsza, Edyta; Dikilitas, Ozan; Kullo, Iftikhar J.; Schaid, Daniel J.; Karlson, Elizabeth W.; Ge, Tian; Meigs, James B.; Smoller, Jordan W.; Lange, Christoph; Crosslin, David R.; Jarvik, Gail P.; Bhatraju, Pavan K.; Hellwege, Jacklyn N.; Chandler, Paulette D.; Torvik, Laura Rasmussen; Fedotov, Alex; Liu, Cong; Kachulis, Christopher; Lennon, Niall J.; Abul‐Husn, Noura S.; Cho, Judy H.; Ionita‐Laza, Iuliana; Gharavi, Ali G.; Chung, Wendy K.; Hripcsak, George; Weng, Chunhua; Nadkarni, Girish N.; Irvin, Marguerite R.; Tiwari, Hemant K.; Limdi, Nita A.; Kiryluk, Krzysztof

doi:10.1038/s41591-022-01869-1

Cited by 85 publications

(72 citation statements)

References 72 publications

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“…Our results are in accordance with the studies conducted [17, 21-24], summarizing that PRS cannot be derived from other ancestry as there can be many differences among the ethnicities in terms of their Linkage Disequilibrium, differences in allele frequencies (variant which is causing risk in one ethnicity might be giving protection to other ethnic group), as a result the PRS would greatly vary as the genetic architecture among ethnic groups varies [17, 25].…”

Section: Introductionsupporting

confidence: 91%

Polygenic Risk Score Comparative Analyses Reveals Risk Disparity of Genetic Predisposition to Chronic Kidney Disease- A Multi Ancestry Approach

Sharma¹,

Sharma²,

Gupta³

et al. 2022

Preprint

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Polygenic Risk Score (PRS) models are used extensively to find the population/individual risk towards disease. These predictive scores are of great help as risk scores if predicted earlier the life of individual can be saved from the chronic/ complex diseases. In this empirical assessments study, the polygenic risk score was calculated in three different ancestries (SAS, EAS and African Americans) based on more than three hundred markers. The risk score we observed indicated that average population risk scores are varied but on cumulating the ancestries the average risk score increased ~1.3 times than individual population average risk. The parameter which varies greatly while calculating the PRS is the ancestry; it should be prerequisite that individuals of same ancestry should be taken as a one population groups while calculating the scores.

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Section: Introductionsupporting

confidence: 91%

Polygenic Risk Score Comparative Analyses Reveals Risk Disparity of Genetic Predisposition to Chronic Kidney Disease- A Multi Ancestry Approach

Sharma¹,

Sharma²,

Gupta³

et al. 2022

Preprint

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“…We performed a combined phenome-wide association analysis using eMERGE-III and UK Biobank (UKBB) datasets (32,33). Details on genotyping and quality control analyses for eMERGE-III and UK Biobank datasets have been described previously (45)(46)(47). The 102,138 genotyped eMERGE-III participants had a total of 20,783 ICD-9 codes mapped to 1,817 distinct phecodes.…”

Section: Meta-phewasmentioning

confidence: 99%

Cell-subtype specific effects of genetic variation in the aging and Alzheimer cortex

Fujita

Gao

Zeng

et al. 2022

Preprint

Self Cite

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The relationship between genetic variation and gene expression in individual brain cell types and subtypes has remained elusive. Here, we generated single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of 424 individuals of advanced age; analyzing 1.5 million nuclear transcriptomes, we assessed the effect of genetic variants on RNA expression incis(cis-eQTL) for 7 cell types and 81 cell subtypes. This effort identified 10,004 eGenes at the cell type level and 8,138 eGenes at the cell subtype level. Many eGenes are only detected within cell subtypes. A new variant influencesAPOEexpression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer pathology, accounting for the effect ofAPOEε4, providing mechanistic insights into both pathologies. While eQTLs are readily detected, only aTMEM106Bvariant robustly affects the proportion of cell subtypes. Integration of these results with GWAS highlighted the targeted cell type and likely causal gene within susceptibility loci for Alzheimer's, Parkinson's, schizophrenia, and educational attainment.

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“…As APOL1 risk variants occur at very low frequency in populations without recent African ancestry (e.g., <0.01% in Europeans, <2% in Latinx), APOL1 is not included in the trans-ancestry PRS. However, APOL1 risk genotype provides additive predictive information to the PRS in African Americans and admixed Latinx [60]. Interestingly, a recent GWAS identified a SNP in the downstream region of DEFB1 , the gene encoding β-defensin-1 (an antimicrobial peptide that is highly expressed in renal tubules), that was associated with 4.4-fold odds of CKD in individuals with APOL1 high risk genotypes but was not independently associated with CKD in those with APOL1 low risk genotypes [61].…”

Section: Host Factors Implicated In the Development And/or Progressio...mentioning

confidence: 99%

Host factors predisposing to kidney disease in people with HIV

Hung

Winkler

Post

2022

Current Opinion in HIV and AIDS

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Purpose of reviewTo highlight advances in understanding of host factors, in particular host genetics, in the development of chronic kidney disease (CKD) in people with HIV. Recent findingsIn Black populations, the G1 and G2 variants of the apolipoprotein L1 (APOL1) gene predispose to HIV-associated nephropathy (HIVAN). The risk of HIVAN is mostly confined to individuals with two APOL1 variants (kidney-risk genotypes). APOL1 kidney-risk genotypes are present in approximately 80% of patients with HIVAN and account for nearly half the burden of end-stage CKD in people of African ancestry with HIV. Progress has been made in elucidating the mechanisms of kidney injury in APOL1 nephropathy, and several targeted molecular therapies are being investigated in clinical trials. Genome-and epigenome-wide association studies are identifying additional genes and pathways that may be involved in the pathogenesis of CKD in people with HIV.

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Genome-wide polygenic score to predict chronic kidney disease across ancestries

Cited by 85 publications

References 72 publications

Polygenic Risk Score Comparative Analyses Reveals Risk Disparity of Genetic Predisposition to Chronic Kidney Disease- A Multi Ancestry Approach

Polygenic Risk Score Comparative Analyses Reveals Risk Disparity of Genetic Predisposition to Chronic Kidney Disease- A Multi Ancestry Approach

Cell-subtype specific effects of genetic variation in the aging and Alzheimer cortex

Host factors predisposing to kidney disease in people with HIV

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