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Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways.

Abstract：

:The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. In the Penn Medicine Biobank, outpatient creatinine measurement-based estimated glomerular filtration rate and multivariable regression models were used to evaluate the association between high-risk APOL1 status and renal outcomes. In meta-analysis of both cohorts, the strongest phenome-wide association study associations were for the high-risk APOL1 variants and diagnoses codes were highly significant for "kidney dialysis" (odds ratio 3.75) and "end stage kidney disease" (odds ratio 3.42). A number of phenotypes were associated with APOL1 high-risk genotypes in an analysis adjusted only for demographic variables. However, no associations were detected with non-renal phenotypes after controlling for chronic/end stage kidney disease status. Using calculated estimated glomerular filtration rate -based phenotype analysis in the Penn Medicine Biobank, APOL1 high-risk status was associated with prevalent chronic/end stage kidney disease /kidney transplant (odds ratio 2.27, 95% confidence interval 1.67-3.08). In high-risk participants, the estimated glomerular filtration rate was 15.4 mL/min/1.73m2; significantly lower than in low-risk participants. Thus, although APOL1 high-risk variants are associated with a range of phenotypes, the risks for other associated phenotypes appear much lower and in our dataset are driven by a primary effect on renal disease.

journal_name

Kidney Int

journal_title

Kidney international

authors

Bajaj A,Ihegword A,Qiu C,Small AM,Wei WQ,Bastarache L,Feng Q,Kember RL,Risman M,Bloom RD,Birtwell DL,Williams H,Shaffer CM,Chen J,Center RG,Denny JC,Rader DJ,Stein CM,Damrauer SM,Susztak K

doi

10.1016/j.kint.2020.01.027

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

1032-1041

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(20)30141-1

journal_volume

pub_type

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Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways.