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DecodeME Lead Variants

As an initial analysis step, we apply GWASLab's procedure for extracting lead variants to the DecodeME GWAS-1 data. This procedure groups together significant genetic variants using a sliding-window approach, then reports the most significant variant in each region.

Table of Variants from GWASLAB

Here is the table of lead variants produced by GWASLab:

SNPID CHR POS EA NEA EAF BETA SE CHISQ MLOG10P N GENE
1:173846152:T:C 1 173846152 C T 0.325279 -0.0759185 0.0136323 31.0138 7.59142 275488 DARS2
6:26239176:A:G 6 26239176 G A 0.261233 0.0825251 0.0140356 34.5711 8.3862 275488 H4C6
6:97984426:C:CA 6 97984426 CA C 0.546314 -0.068408 0.0125368 29.7742 7.3139 275488 MMS22L
15:54866724:A:G 15 54866724 G A 0.311707 0.0785482 0.0135977 33.369 8.11788 275488 UNC13C
17:52183006:C:T 17 52183006 T C 0.329679 0.0805953 0.0134577 35.8658 8.67492 275488 CA10
20:48914387:T:TA 20 48914387 TA T 0.633808 0.0909054 0.0133414 46.4275 11.0219 275488 ARFGEF2

Note that the genomic coordinates in the table above refer to genome build 38.

Comparison with lead variants reported in DecodeME

The lead variants reported above by GWASLAB all agree with the variants reported by the DecodeME preprint1. However, in some cases, GWASLAB assigns these lead variants to different genes than the DecodeME preprint.

In particular

  • 17:52183006:C:T is assigned to CA10 by both GWASLAB and the DecodeME preprint.
  • 20:48914387:T:TA is assigned to both ARFGEF2 and CSE1L by the DecodeME preprint. GWASLAB assigns only ARFGEF2.
  • The other variants are assigned to different genes by GWASLAB and the DecodeME preprint. This reflects ambiguity about how to assign GWAS signals to genes.

Reproducing

To reproduce this analysis, run the initial DecodeME analysis script.

  1. Genetics Delivery Team, Thibaud Boutin, Andrew D Bretherick, Joshua J Dibble, Esther Ewaoluwagbemiga, Emma Northwood, Gemma L Samms, Veronique Vitart, Project, Cohort Delivery Team, Øyvind Almelid, and others. Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. medRxiv, pages 2025–08, 2025. URL: https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1. ↩