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. 2019 Jan 15;8:e39856. doi: 10.7554/eLife.39856

Figure 2. Validation of SNPs identified in other studies using independent samples of European descent.

Discovery – Candidate SNPs or proxies (r2 > 0.95) associated with lifespan (top panels, stratified by sex) and longevity (bottom panel) by previous studies (Zeng et al., 2016; Pilling et al., 2017; Deelen et al., 2014; Flachsbart et al., 2009; Sebastiani et al., 2017; Ben-Avraham et al., 2017). Effect sizes have been rescaled to years of life to make direct comparisons between studies (see Materials and methods and Figure 2—figure supplement 1). Replication – Independent samples, either the LifeGen meta-analysis to replicate Pilling et al. (2017), or the full dataset including UK Biobank. Gene names are as reported by discovery and have been coloured based on overlap between confidence intervals (CIs) of effect estimates. Dark blue – Nominal replication (p < 0.05, one-sided test). Light blue – CIs overlap (Phet > 0.05) and cover zero, but replication estimate is closer to discovery than zero. Yellow – CIs overlap (Phet > 0.05) and cover zero, and replication estimate is closer to zero than discovery. Red – CIs do not overlap (Phet < 0.05) and replication estimate covers zero. Black – no replication data.

Figure 2—source data 1. Eight candidate lifespan regions replicate nominally (p < 0.05) in LifeGen or our full sample.
Listed are SNPs or close proxies (r2 > 0.95), which have been previously reported to associate with lifespan or extreme longevity. At or near – Gene, cluster of genes, or cytogenetic band in close proximity to lead SNP; Chr – Chromosome, Position – Base-pair position on chromosome (build GRCh37); A1 – the effect allele, increasing lifespan in discovery; Freq1- Frequency of the A1 allele in the replication sample, or if missing, the discovery sample; Sex – sex of the individuals or their parents used in the discovery and replication; Beta1 – the loge(protection ratio) for carrying one copy of A1 under additive dosage model, inferred for discovery (see Materials and methods); SE – Standard Error, calculated from reported P value and inferred effect estimates for discovery, assuming a two-sided test; Years – Years of lifespan gained for carrying one copy of the A1 allele; P – P value reported by original study for discovery, one-sided P value for the Wald test association between imputed dosage and cox model residual for the replication. For discovery, except Pilling et al’s SNPs (Pilling et al., 2017), where we re-calculated effects directly from individual UKBB data ourselves, effects sizes have been converted to a common scale to enable comparison. Study – original study that identified the candidate SNP; Sample – independent sample used to replicate the results (a = Full dataset, b = LifeGen excluding UK Biobank). Loci showing nominal replication (p < 0.05) are bolded.
elife-39856-fig2-data1.xlsx (14.5KB, xlsx)
DOI: 10.7554/eLife.39856.010

Figure 2.

Figure 2—figure supplement 1. Concordance between inferred effect sizes from Pilling et al. (2017) and our estimated effect sizes in a largely overlapping UK Biobank sample.

Figure 2—figure supplement 1.

Effect estimates from Pilling et al. (2017) were converted to loge(protection ratio) based solely on the proportion dead in individual parental samples, or (for combined parents results) based on an empirical conversion factor from APOE (see Materials and methods). By definition, the inferred effect estimate for APOE in combined parents is identical between the studies; all other estimates provide a measure of concordance between inferred and calculated effects for each locus. Gene names are as reported by discovery. Note, rs161091095 near USP2–AS1 is a proxy (r2 = 1.00) for rs139137459, the SNP reported by Pilling et al. No proxies could be found for 13:31871514_T_G. Gene – Nearby gene(s) as reported by discovery. SNP – rsID of SNP or proxy. A1 – Longevity allele. Beta - the estimated loge(protection ratio) for one copy of the effect allele. CI – Confidence Interval.