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Chr20 47M-48.2M

Methodology

To narrow the DecodeME1 GWAS-1 signal, I fine-mapped the hit on chromosome 20 using SUSIE2. The parameters of my SUSIE runs were the same as for the chromosome 1 locus.

Results

At the chromosome 20 locus, the \(L=10\) SUSIE run returned two credible sets. One of these credible sets is highly concentrated, consisting of a single \(\mathrm{PIP}=1.0\) variant. In contrast, the three other SUSIE runs return a single diffuse credible set. Given that the concentrated credible set is absent from the SUSIE runs with regularization, I am inclined to discount it as an artifact, possibly resulting from a slight mismatch between the population used to generate the GWAS summary statistics and the population used to create the LD matrix. It would be interesting to re-run SUSIE on this locus using individual-level data to confirm or refute this explanation.

The UpSet plot for this locus reveals that the variants found by the \(L=10\) SUSIE run differ from those found by other runs.

chr20_upset_plot

The Stackplot and variant list for the \(L=10\) run shows the highly concentrated nature of one of the credible sets.

chr20_l10

Variant List (L=10)
cs CHR POS EA NEA alpha mu PIP
L2 20 47743125 A C 1 0.0465541 1
L3 20 47731228 C A 0.0942816 -0.058085 0.0942816
L3 20 47731158 C T 0.0277448 -0.0577275 0.0277448
L3 20 47779340 C T 0.0271773 -0.0577214 0.0271773
L3 20 47783770 TG T 0.0259644 -0.057708 0.0259644
L3 20 47792457 C A 0.0232865 -0.0576761 0.0232865
L3 20 47727079 A G 0.0228546 -0.0576706 0.0228546
L3 20 47789849 G C 0.0207733 -0.0576426 0.0207733
L3 20 47717405 C T 0.0205823 -0.0576399 0.0205823
L3 20 47721937 T TTTG 0.0201703 -0.0576339 0.0201703
L3 20 47687238 T TG 0.0179336 0.0575994 0.0179336
L3 20 47739415 T C 0.0175571 -0.0575932 0.0175571
L3 20 47750377 A C 0.0174729 -0.0575918 0.0174729
L3 20 47776919 T A 0.0159528 -0.057565 0.0159528
L3 20 47808070 A G 0.0156314 -0.057559 0.0156314
L3 20 47703810 A C 0.0156019 -0.0575585 0.0156019
L3 20 47770756 C A 0.0135108 -0.0575162 0.0135108
L3 20 47751708 A AAAG 0.0134858 -0.0575156 0.0134858
L3 20 47721385 A G 0.0127438 -0.057499 0.0127438
L3 20 47621372 A G 0.0123093 0.0574888 0.0123093
L3 20 47725607 G A 0.0118942 -0.0574787 0.0118942
L3 20 47762700 A G 0.0118404 -0.0574773 0.0118404
L3 20 47741556 T C 0.0118239 -0.0574769 0.0118239
L3 20 47720386 C G 0.0113099 -0.0574638 0.0113099
L3 20 47701339 G A 0.0112238 -0.0574616 0.0112238
L3 20 47692392 C T 0.0105991 0.0574447 0.0105991
L3 20 47815944 C T 0.0102166 -0.0574339 0.0102166
L3 20 47728829 G GCTTA 0.0101749 -0.0574327 0.0101749
L3 20 47727341 G A 0.00978623 -0.0574212 0.00978623
L3 20 47646210 C G 0.00951013 0.0574128 0.00951013
L3 20 47676281 A G 0.00926458 -0.057405 0.00926458
L3 20 47758549 T C 0.00924127 -0.0574043 0.00924127
L3 20 47695391 A G 0.00890339 -0.0573933 0.00890339
L3 20 47714214 C T 0.00874825 -0.0573881 0.00874825
L3 20 47690591 G T 0.00862875 0.0573841 0.00862875
L3 20 47819305 A G 0.00851096 -0.05738 0.00851096
L3 20 47792245 T C 0.0082753 -0.0573717 0.0082753
L3 20 47714370 C T 0.00811626 -0.057366 0.00811626
L3 20 47739814 T C 0.00810486 -0.0573656 0.00810486
L3 20 47820626 T G 0.00801292 -0.0573622 0.00801292
L3 20 47541600 A G 0.00785385 0.0573563 0.00785385
L3 20 47719810 A G 0.00774204 -0.0573521 0.00774204
L3 20 47719949 C T 0.00763449 -0.057348 0.00763449
L3 20 47663944 C G 0.00755216 0.0573448 0.00755216
L3 20 47718431 G C 0.00739525 -0.0573386 0.00739525
L3 20 47783095 C T 0.00734969 -0.0573367 0.00734969
L3 20 47718594 C T 0.00733531 -0.0573362 0.00733531
L3 20 47726129 C T 0.00731401 -0.0573353 0.00731401
L3 20 47663382 G A 0.00718852 0.0573302 0.00718852
L3 20 47713063 T C 0.00715927 -0.057329 0.00715927
L3 20 47720957 C T 0.00686221 -0.0573165 0.00686221
L3 20 47820667 A T 0.00669051 -0.057309 0.00669051
L3 20 47710558 A ACAG 0.00659105 -0.0573046 0.00659105
L3 20 47769837 AT A 0.00655973 -0.0573032 0.00655973
L3 20 47769838 G C 0.00655973 -0.0573032 0.00655973
L3 20 47692827 C T 0.00644522 0.057298 0.00644522
L3 20 47721723 CAGG C 0.00633593 -0.0572929 0.00633593
L3 20 47690139 C T 0.00630622 0.0572915 0.00630622
L3 20 47714291 G A 0.00620647 -0.0572868 0.00620647
L3 20 47782356 C CCT 0.00616044 -0.0572846 0.00616044
L3 20 47721759 C T 0.00582328 -0.057268 0.00582328
L3 20 47635715 A G 0.00578918 0.0572663 0.00578918
L3 20 47554392 G A 0.00569192 0.0572613 0.00569192
L3 20 47737958 C A 0.00560748 -0.0572568 0.00560748
L3 20 47739193 A G 0.00558553 -0.0572557 0.00558553
L3 20 47667056 T C 0.00557469 -0.0572551 0.00557469
L3 20 47749296 C CCAAAA 0.00535179 -0.057243 0.00535179
L3 20 47774166 G A 0.00525087 -0.0572374 0.00525087
L3 20 47724325 G C 0.00505351 -0.0572261 0.00505351
L3 20 47771274 A G 0.00495579 -0.0572203 0.00495579
L3 20 47645427 T G 0.00488911 0.0572163 0.00488911
L3 20 47690189 A G 0.00473993 0.0572071 0.00473993
L3 20 47798664 C T 0.00468602 -0.0572037 0.00468602
L3 20 47795784 C CA 0.0045752 -0.0571967 0.0045752
L3 20 47653364 CTTTG C 0.00454497 0.0571947 0.00454497
L3 20 47543604 A G 0.00448422 0.0571907 0.00448422
L3 20 47549979 T TA 0.00446201 0.0571893 0.00446201
L3 20 47678770 G A 0.00429819 0.0571782 0.00429819
L3 20 47725800 C CTG 0.00426857 -0.0571761 0.00426857
L3 20 47675525 A G 0.00423721 -0.057174 0.00423721
L3 20 47753019 T C 0.00423611 -0.0571739 0.00423611
L3 20 47760000 C T 0.00416406 -0.0571688 0.00416406
L3 20 47677017 GA G 0.00409319 -0.0571637 0.00409319
L3 20 47748375 A G 0.0039907 -0.0571562 0.0039907
L3 20 47673230 GTTT G 0.00388325 0.0571481 0.00388325
L3 20 47755742 T C 0.00384134 -0.0571449 0.00384134
L3 20 47766197 C T 0.00383843 -0.0571447 0.00383843
L3 20 47797653 A G 0.00380894 -0.0571424 0.00380894
L3 20 47755075 A G 0.00372042 -0.0571354 0.00372042
L3 20 47662823 G T 0.00368736 0.0571328 0.00368736
L3 20 47766929 T C 0.00363455 -0.0571285 0.00363455
L3 20 47774343 A G 0.00359647 -0.0571254 0.00359647
L3 20 47757963 T C 0.00342714 -0.0571111 0.00342714
L3 20 47763558 A C 0.00340866 -0.0571095 0.00340866
L3 20 47746627 AATAG A 0.00340309 -0.057109 0.00340309
L3 20 47818567 T C 0.00337018 -0.0571062 0.00337018
L3 20 47758719 A G 0.00335916 -0.0571052 0.00335916
L3 20 47640466 G C 0.00331296 0.0571011 0.00331296
L3 20 47769157 A G 0.00322367 -0.057093 0.00322367
L3 20 47647068 A G 0.00310123 0.0570815 0.00310123
L3 20 47648854 T C 0.00310093 0.0570815 0.00310093
L3 20 47745084 C G 0.00303794 -0.0570754 0.00303794
L3 20 47753265 T C 0.00300333 -0.057072 0.00300333

In contrast, the stackplot and variant list for \(L=2\) reveal a single credible set

chr20_L2

This region of chromosome 20 is relatively gene-dense, so that are a number of plausible causal genes.

Variant List (L=2)
cs CHR POS EA NEA alpha mu PIP
L1 20 47530924 TA T 0.0942184 0.027463 0.0942184
L1 20 47530801 T TTGC 0.0900384 0.0274356 0.0900384
L1 20 47532999 G A 0.0827506 0.0273843 0.0827506
L1 20 47530037 C T 0.0776545 0.0273457 0.0776545
L1 20 47529913 T C 0.074241 0.0273184 0.074241
L1 20 47533655 C T 0.0718805 0.0272987 0.0718805
L1 20 47531606 C T 0.0718423 0.0272984 0.0718423
L1 20 47535298 C A 0.0655834 0.0272428 0.0655834
L1 20 47527742 C A 0.0655829 0.0272428 0.0655829
L1 20 47523865 C A 0.0640172 0.027228 0.0640172
L1 20 47526493 G T 0.0636458 0.0272245 0.0636458
L1 20 47530150 T C 0.0478056 0.0270491 0.0478056
L1 20 47731228 C A 0.00433327 -0.0255305 0.00433327
L1 20 47731158 C T 0.00209394 -0.0250523 0.00209394
L1 20 47779340 C T 0.00206127 -0.0250418 0.00206127
L1 20 47783770 TG T 0.00200365 -0.025023 0.00200365
L1 20 47792457 C A 0.00191728 -0.0249937 0.00191728
L1 20 47717405 C T 0.00183741 -0.0249654 0.00183741
L1 20 47721937 T TTTG 0.00179731 -0.0249507 0.00179731
L1 20 47789849 G C 0.00177923 -0.0249439 0.00177923
L1 20 47623827 CT C 0.00170185 0.0249143 0.00170185
L1 20 47703810 A C 0.00169575 -0.0249119 0.00169575
L1 20 47739415 T C 0.00168367 -0.0249071 0.00168367
L1 20 47687238 T TG 0.00168216 0.0249065 0.00168216
L1 20 47701339 G A 0.00166606 -0.0249001 0.00166606
L1 20 47808070 A G 0.00166435 -0.0248994 0.00166435
L1 20 47750377 A C 0.00162562 -0.0248837 0.00162562
L1 20 47776919 T A 0.00162064 -0.0248816 0.00162064
L1 20 47770756 C A 0.00153315 -0.0248445 0.00153315
L1 20 47621372 A G 0.00147649 0.0248193 0.00147649
L1 20 47751708 A AAAG 0.00146798 -0.0248154 0.00146798
L1 20 47721385 A G 0.00145078 -0.0248075 0.00145078
L1 20 47815944 C T 0.00140705 -0.024787 0.00140705
L1 20 47762700 A G 0.00140424 -0.0247856 0.00140424
L1 20 47820626 T G 0.00140143 -0.0247843 0.00140143
L1 20 47551632 CTCTTTTTT C 0.00136966 0.0247689 0.00136966
L1 20 47819305 A G 0.00136573 -0.024767 0.00136573
L1 20 47646210 C G 0.00131549 0.0247418 0.00131549
L1 20 47820667 A T 0.00130599 -0.0247369 0.00130599
L1 20 47727079 A G 0.00128907 -0.0247282 0.00128907
L1 20 47676281 A G 0.00128729 -0.0247272 0.00128729
L1 20 47769838 G C 0.00127763 -0.0247222 0.00127763
L1 20 47769837 AT A 0.00127763 -0.0247222 0.00127763
L1 20 47677017 GA G 0.00125172 -0.0247084 0.00125172
L1 20 47758549 T C 0.00124844 -0.0247066 0.00124844
L1 20 47792245 T C 0.00122507 -0.0246939 0.00122507
L1 20 47663382 G A 0.00118616 0.0246722 0.00118616
L1 20 47645427 T G 0.00098997 0.02455 0.00098997
L1 20 47783095 C T 0.00096882 -0.0245354 0.00096882
L1 20 47725607 G A 0.000941141 -0.0245157 0.000941141
L1 20 47741556 T C 0.000935673 -0.0245117 0.000935673
L1 20 47795784 C CA 0.000925569 -0.0245044 0.000925569
L1 20 47720386 C G 0.000924296 -0.0245034 0.000924296
L1 20 47782356 C CCT 0.000911758 -0.0244942 0.000911758
L1 20 47728829 G GCTTA 0.000898548 -0.0244843 0.000898548
L1 20 47818567 T C 0.000888571 -0.0244767 0.000888571
L1 20 47744691 GA G 0.000882511 -0.024472 0.000882511
L1 20 47692392 C T 0.000862608 0.0244565 0.000862608
L1 20 47769939 TA T 0.000856973 -0.0244521 0.000856973
L1 20 47774166 G A 0.000856318 -0.0244515 0.000856318
L1 20 47727341 G A 0.000854931 -0.0244504 0.000854931
L1 20 47714214 C T 0.000843545 -0.0244413 0.000843545
L1 20 47541600 A G 0.000842737 0.0244407 0.000842737
L1 20 47749296 C CCAAAA 0.000837409 -0.0244364 0.000837409
L1 20 47771274 A G 0.000836275 -0.0244354 0.000836275
L1 20 47798664 C T 0.000823076 -0.0244246 0.000823076
L1 20 47663944 C G 0.000819583 0.0244217 0.000819583
L1 20 47714370 C T 0.000818408 -0.0244207 0.000818408
L1 20 47695391 A G 0.000800477 -0.0244056 0.000800477
L1 20 47739814 T C 0.000795636 -0.0244015 0.000795636
L1 20 47760856 G A 0.000791101 -0.0243976 0.000791101
L1 20 47690591 G T 0.000790097 0.0243968 0.000790097
L1 20 47760857 C G 0.00078917 -0.0243959 0.00078917
L1 20 47719810 A G 0.000787046 -0.0243941 0.000787046
L1 20 47753019 T C 0.000786678 -0.0243938 0.000786678

  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. ↩

  2. Gao Wang, Abhishek Sarkar, Peter Carbonetto, and Matthew Stephens. A simple new approach to variable selection in regression, with application to genetic fine mapping. Journal of the Royal Statistical Society Series B: Statistical Methodology, 82(5):1273–1300, 2020. URL: https://academic.oup.com/jrsssb/article/82/5/1273/7056114. ↩