Table 1 GWAS results. Summary information on the lead variants identified from each GWAS analysis and the significant genes from the LoF analysis. For each significant locus across the three diastolic phenotypes, variant information, GWAS summary statistics and variant to gene annotation is provided. The evidence column is split by MS; eQTL (colocalization between the GWAS signal and an eQTL for the gene in a plausible tissue type) (Supplementary Material); M (plausible mechanistic link between the gene and the measured heart phenotypes that is the gene function suggests a link to diastolic function); and Overall (the confidence of variant to gene mapping given all the available evidence). Loci highlighted in gray are those that reached genome-wide significance in the discovery, validation and full datasets, loci in white reach suggestive significance in the discovery dataset and genome-wide significance in the full dataset. Further information is provided in the Supplementary Material. Chr, chromosome; ref, reference allele; Alt, alternative allele; MAF, minor allele frequency; Disc, discovery; Repl, replication; MS, missense variant; eQTL, expression quantitative trait loci.
From: Genetic and environmental determinants of diastolic heart function
Lead variant | GWAS | Annotation | Evidence | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
rsIDFull | Chr | Ref | Alt | MAF | Phenotype | EstimateFull | SEFull | PFull | Disc | Repl | Full | Locus genes | Closest gene | Likely causal gene | MS | eQTL | M | Overall |
10 | T | C | 0.21 | PDSRrr | 0.1118 | 0.0175 | 2.3 × 10−10 | Y | Y | Y | MCMBP, BAG3 | BAG3 | BAG3 | Y | Y | Y | High | |
18 | T | C | 0.28 | PDSRrr/PDSRll | 0.1087 | 0.0164 | 1.7 × 10−11 | Yrr | Y | Y | FHOD3, TPGS2 | FHOD3 | FHOD3 | N | Y | Y | High | |
6 | C | T | 0.45 | PDSRll | 0.0278 | 0.0043 | 1.9 × 10−10 | Y | Y | Y | PLN, CEP85L, SLC35F1 | PLN | PLN | N | Y | Y | High | |
12 | C | A | 0.46 | PDSRrr/PDSRll | 0.0807 | 0.0146 | 4.1 × 10−8 | Yrr | Y | Y | AC023158.2, AC023158.1, ALG10 | AC023158.2 | AC023158.1 | N | Y | N | Low | |
2 | C | T | 0.23 | LAVmaxi | 0.0117 | 0.0020 | 5.3 × 10−9 | Y | Y | Y | Multiple | EFEMP1 | EFEMP1 | N | Y | N | Low | |
5 | T | C | 0.40 | LAVmaxi | 0.0096 | 0.0017 | 1.7 × 10−8 | N | N | Y | NPR3, LINC02120 | LINC02120 | NPR3 | N | Y | Y | High | |
6 | C | T | 0.11 | PDSRrr | −0.1413 | 0.0244 | 8.4 × 10−9 | N | N | Y | HSF2, GJA1, SERINC1 | GJA1 | GJA1 | N | Y | Y | Medium | |
7 | T | C | 0.18 | PDSRll | 0.0336 | 0.0056 | 1.2 × 10−9 | N | N | Y | NDUFA4, PHF14 | PHF14 | PHF14 | N | Y | Y | Medium | |
12 | C | T | 0.43 | PDSRrr | 0.0872 | 0.0146 | 3.9 × 10−9 | N | N | Y | Multiple | SP1 | SP1 | N | Y | N | Low | |
Predicted LoF results | ||||||||||||||||||
Chr | Carriers | Phenotype | EstimateFull | SEFull | PFull | Causal gene | MS | M | Overall | |||||||||
2 | 187 | PDSRrr | −0.71 | 0.14 | 1.4 × 10−7 | TTN | Y | Y | High | |||||||||
6 | 29 | PDSRrr | −1.56 | 0.34 | 5.6 × 10−6 | LMBRD1 | Y | ? | High | |||||||||
