Table 4 Genes supported as likely causal genes in decline-associated or stable-effect loci

From: Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline

Gene

Index variant: location (probability to be causal)

Index variant: functional consequence

Known phenotype

Locus type and novelty

Genes mapped to decline-associated loci

UMOD

Near/in gene (100%, 13%, 6%)a

eQTL(+)

Mendelianb

Novel 3rd signal

TPPP

Nearest (90%)

eQTL(+)

 

Known decline

FGF5

Nearest (49%)

eQTL(−)

 

Known decline

PRKAG2

In gene (80%)

 

Mendelianc

Known decline

SDCCAG8

In gene (22%)

 

Mendeliand

Novel decline

RRAGD

In gene (93%)

5′ UTR

Mendeliane

Novel decline

Genes mapped to stable-effect loci

CPS1

In gene (100%)

Missense

Creatinine

Stable effect

SLC22A2

In gene (43%)

 

Creatinine

Stable effect

SLC34A1

in gene (100%)

 

Mendelianf

Stable effect

UNCX

Nearest (61%)

eQTL(+)

 

Stable effect

  1. We annotated 256 and 182 genes in 10 decline-associated and 9 stable-effect loci, respectively, for statistical and biological features: known human kidney disease (OMIM59 and other39,60); drug target61; gene nearest to index variant62,67; mapped by variant >10% statistically likely causal23 that altered protein, protein abundancy, or gene expression in kidney tissue37,63,64 (eQTL, ± indicating up/downregulation by eGFR-lowering allele; “Methods” section, Supplementary Data 6 and Supplementary Note 3). Shown are the 10 genes with ≥3 features that supported the gene as likely causal for the association, indicating key information on index variant (location, probability to be causal, functional consequence), gene (human kidney phenotype or role in creatinine metabolism), and locus (known or novel for decline association, stable-effect locus).
  2. eQTL expression quantitative trait locus in kidney tissue, 5′ UTR 5′ untranslated region.
  3. aThree independent index variants in UMOD/PDILT locus.
  4. bADTKD (autosomal dominant tubulo-interstitial kidney disease).
  5. cGlycogen storage disease of heart with kidney involvement (renomegaly).
  6. dBardet-Biedl syndrome 16 (retina-renal ciliopathy).
  7. eRenal hypomagnesemia 7.
  8. fFanconi Renotubular Syndrome 2.
Back to article page