Fig. 4

Extraction and meta-analysis of two top loci from Cai et al. [17] from study groups in this GWAS. SNPs for two loci identified in a GWAS of in silico estimated mtDNA CN were extracted from each of the study groups in this cohort (NB: a smaller subset of 2833 ALSPAC mothers were used, since there were mother-child duos present between the original study group of 5461 and the two groups of ALSPAC children) total N = 11,253. Columns: SNP = rsID; gene = gene name; group = study group, beta = effect size; LCI/UCI = 95% confidence interval (lower, then upper bound); P = p value; and I² = I² metric for heterogeneity. Meta-analyses were by random-effects and are shown as black diamonds. For reference, the ALSPAC estimate from Cai et al. [17] is shown for each locus. This replication group included ALSPAC 6–9-year-olds (with mtDNA CN assayed from sequence data). Betas had to be harmonised, as those in Cai et al. [17] were given as SD change in mtDNA CN per SD increase in genotype. SD of genotype was estimated from allele frequencies provided for the cohort by Cai et al. [17] given as 0.342 for rs445 and 0.169 for rs11006126 (in the supplement of this paper). SDs were then calculated as √(2 × (1-MAF) × MAF) (evaluating to 0.53 and 0.67 for rs11006126 and rs445, respectively). Betas and standard errors were then transformed from those given in Table 1 of Cai et al. to a ‘per risk allele’ scale, by multiplying the given beta by (1/the estimated SD), i.e. rs11006126 = 0.179 × (1/0.53); rs445 = 0.110 × (1/0.67). CaiALSPAC = result from Cai et al. [17]. UKBSF/UKBSM = females and males in UKBS cohort