Fig. 2: Meta-analysis of 11 GWAS studies of long COVID shows an association at the FOXP4 locus.
a, Manhattan plot of long COVID after test-verified SARS-CoV-2 infection (strict case definition, n = 3,018) compared to all other individuals in each dataset (population controls, broad control definition, n = 994,582). A genome-wide significant association with long COVID was found in the chromosome 6, upstream of the FOXP4 gene (chr6: 41,515,652 G:C, GRCh38, rs9367106, as the lead variant; P = 1.76 × 10−10, Bonferroni P = 7.06 × 10−10, increased risk with the C allele, OR = 1.63, 95% CI = 1.40–1.89). Horizontal lines indicate genome-wide significance thresholds for IVW meta-analysis before (P < 5 × 10−8, dashed line) and after (1.25 × 10−8) Bonferroni correction over the four long COVID meta-analyses (INCMNSZ = MexGen-COVID Initiative). b, Chromosome 6 lead variant across the contributing studies and ancestries in GWAS meta-analyses of long COVID with strict case definition and broad control definition. Lead variant rs9367106 (solid line) and if missing, imputed by the variant with the highest LD with the lead variant for illustrative purpose, that is, rs12660421 (r = 0.98 in European in 1,000 G + HGDP samples55, dotted lines). For the imputed variants, β was weighted by multiplying by the LD correlation coefficient (r = 0.98). Centre, OR; error bar, 95% CI. Genetic ancestries marked by colors. MAF varies across ancestries, ranging from 1% to 34% (Supplementary Fig. 4). AFR, African; AMR, Admixed American; EAS, East Asian; EUR, European; UKBB, UK Biobank. (Results for the other three GWAS meta-analyses in Supplementary Figs. 2 and 3a–c).
