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Chr6 97.5M-99M

Methodology

To narrow the DecodeME1 GWAS-1 signal, I fine-mapped the second hit on chromosome 6 using SUSIE2. The parameters of my SUSIE runs were the same as for the chromosome 1 locus.

Results

The 4 SUSIE runs each produced a single credible set containing 98 variants. These credible sets were largely but not entirely overlapping:

chr6b_upsetplot

The stacked plot for the \(L=10\) run:

ch6b_stackplot

And for the \(L=2\) run:

chrb_stackplot_l2

Overall, SUSIE returns a diffuse signal in a region rather far from genes, making the genetic mechanism of action non-obvious.

The variants in the credibles set for the \(L=10\) and \(L=2\) runs are listed below:

Variant List (L=10)
cs CHR POS EA NEA alpha mu PIP
L1 6 98432302 CA C 0.0339333 -0.0209021 0.0340642
L1 6 98537993 A G 0.0319325 -0.0208545 0.0319893
L1 6 98537145 G A 0.0288642 -0.0207752 0.0289191
L1 6 98542303 C T 0.0256115 0.020681 0.0256655
L1 6 98535730 C G 0.0250234 -0.0206626 0.0250771
L1 6 98540357 A T 0.023551 0.0206146 0.0236042
L1 6 98431805 G A 0.0215665 -0.0205447 0.0216144
L1 6 98398914 C T 0.0204441 -0.0205022 0.0204915
L1 6 98394217 C G 0.0192989 -0.0204562 0.0193461
L1 6 98448725 A G 0.0192954 -0.0204561 0.0193439
L1 6 98436938 A G 0.0189514 -0.0204417 0.0189984
L1 6 98402387 C G 0.0189412 -0.0204412 0.0189882
L1 6 98444794 A C 0.0189194 -0.0204403 0.0189676
L1 6 98390677 G T 0.0182881 -0.0204132 0.018335
L1 6 98489654 T C 0.0173721 -0.020372 0.0175614
L1 6 98390463 A T 0.0174165 -0.0203741 0.017463
L1 6 98400834 T C 0.0172352 -0.0203657 0.0172816
L1 6 98390699 G C 0.0172085 -0.0203644 0.0172555
L1 6 98403406 T C 0.0168904 -0.0203494 0.0169366
L1 6 98388730 T C 0.0165388 -0.0203325 0.016585
L1 6 98448405 A C 0.0160753 -0.0203097 0.0161225
L1 6 98392312 C T 0.0155774 -0.0202844 0.0156232
L1 6 98437655 A AC 0.0145205 -0.0202277 0.0145671
L1 6 98434438 T C 0.0143232 -0.0202166 0.0143697
L1 6 98419613 T C 0.0139924 -0.0201978 0.0140375
L1 6 98412564 C T 0.0137653 -0.0201845 0.0138103
L1 6 98436333 T A 0.0135699 -0.0201729 0.013616
L1 6 98366735 G A 0.0123164 -0.0200943 0.0125522
L1 6 98416456 T C 0.0118428 -0.0200624 0.0118877
L1 6 98450190 A T 0.0118003 0.0200594 0.0118451
L1 6 98416458 T C 0.011667 -0.0200502 0.0117119
L1 6 98392511 T TTA 0.01063 -0.0199742 0.0106739
L1 6 98416821 C A 0.0102941 -0.0199479 0.0103376
L1 6 98417147 T A 0.00984921 -0.0199117 0.00989241
L1 6 98438566 T A 0.0088468 -0.0198234 0.00891711
L1 6 98433708 C A 0.00877593 -0.0198168 0.00884611
L1 6 98413299 T C 0.00854076 -0.0197944 0.00858394
L1 6 98439152 A T 0.0085006 -0.0197905 0.00857027
L1 6 98426502 G A 0.00838434 -0.0197791 0.00842742
L1 6 98437775 C T 0.00821572 -0.0197623 0.00828487
L1 6 98445008 A C 0.00811219 -0.0197518 0.00818105
L1 6 98431600 T C 0.00807156 -0.0197477 0.00814043
L1 6 98509711 A G 0.00785555 -0.0197252 0.00792232
L1 6 98403022 T C 0.00713891 -0.0196458 0.00720467
L1 6 98401847 C T 0.00642492 -0.019558 0.00649023
L1 6 98395421 A C 0.00640626 -0.0195556 0.00647165
L1 6 98398945 G A 0.00638722 -0.0195531 0.00645239
L1 6 98396176 A G 0.00626519 -0.019537 0.00633014
L1 6 98399604 C T 0.0062293 -0.0195322 0.00629421
L1 6 98398832 T C 0.00622043 -0.019531 0.00628523
L1 6 98401483 C A 0.00616394 -0.0195233 0.00622867
L1 6 98405151 A T 0.00613886 -0.0195199 0.0062035
L1 6 98396351 G A 0.00613873 -0.0195199 0.0062034
L1 6 98399612 A T 0.00612351 -0.0195178 0.00618817
L1 6 98415905 T C 0.00609124 -0.0195134 0.00615491
L1 6 98399407 T C 0.00605283 -0.0195081 0.00611723
L1 6 98405214 G C 0.00604532 -0.0195071 0.00610974
L1 6 98406939 A G 0.0060202 -0.0195036 0.00608459
L1 6 98401808 C T 0.00597186 -0.0194968 0.00603611
L1 6 98398843 A AT 0.00586082 -0.0194811 0.00592683
L1 6 98403903 C T 0.00584561 -0.0194789 0.00590957
L1 6 98402211 T G 0.00575721 -0.0194661 0.00582099
L1 6 98405337 G C 0.00567947 -0.0194547 0.00574303
L1 6 98406850 C T 0.0055801 -0.0194399 0.00564347
L1 6 98402394 C A 0.0055769 -0.0194394 0.00564045
L1 6 98402438 C T 0.00556739 -0.019438 0.00563084
L1 6 98397820 T C 0.00548189 -0.0194249 0.00554499
L1 6 98404174 C T 0.00546584 -0.0194225 0.00552887
L1 6 98404346 C T 0.00539529 -0.0194115 0.00545816
L1 6 98418637 C T 0.00534217 -0.0194032 0.00540408
L1 6 98546394 C T 0.00528216 0.0193937 0.0053302
L1 6 98423208 A G 0.00525697 -0.0193897 0.00531947
L1 6 98416581 C A 0.00494431 -0.0193379 0.00500522
L1 6 98415577 G T 0.00492045 -0.0193338 0.00498232
L1 6 98419195 G A 0.00463716 -0.0192837 0.00469802
L1 6 98410756 A G 0.00462844 -0.0192821 0.00468929
L1 6 98517804 T G 0.00442417 -0.0192438 0.00446464
L1 6 98522102 A C 0.00441152 -0.0192414 0.00445198
L1 6 98456578 C T 0.00432927 0.0192254 0.00436958
L1 6 98476651 G T 0.00432493 0.0192245 0.00436525
L1 6 98518138 C CCAGGTACTGAAAATAGTACCCA 0.00425748 -0.0192112 0.00429785
L1 6 98517272 A G 0.00418293 -0.0191961 0.00422317
L1 6 98510530 T G 0.00397918 -0.0191536 0.00401923
L1 6 98511568 T C 0.0039301 -0.019143 0.00397007
L1 6 98512865 T C 0.00392975 -0.0191429 0.00396971
L1 6 98502762 A G 0.00391319 -0.0191393 0.00395313
L1 6 98453465 C T 0.00382927 -0.0191208 0.0038691
L1 6 98500715 G A 0.0036407 -0.0190776 0.00368034
L1 6 98486851 G A 0.00351126 -0.0190466 0.00355074
L1 6 98473185 A G 0.00348687 0.0190406 0.00352693
L1 6 98449707 A G 0.00323224 0.0189754 0.00327213
L1 6 98473269 A C 0.00317038 0.0189588 0.00321004
L1 6 98488771 G A 0.00308858 -0.0189362 0.00312758
L1 6 98460173 C G 0.00268056 0.0188136 0.00271956
L1 6 98449775 T TATA 0.0024706 0.0187426 0.00252651
L1 6 98494482 T C 0.0022754 -0.0186707 0.00231381
L1 6 98493740 T A 0.00216464 -0.018627 0.00220288
L1 6 98493210 G T 0.00198909 0.0185527 0.00202701
Variant List (L=2)
cs CHR POS EA NEA alpha mu PIP
L1 6 98432302 CA C 0.0530686 -0.0216425 0.0530686
L1 6 98537993 A G 0.0248035 -0.0210597 0.0248035
L1 6 98537145 G A 0.0225441 -0.0209853 0.0225441
L1 6 98542303 C T 0.0200106 0.0208922 0.0200106
L1 6 98535730 C G 0.0195324 -0.0208732 0.0195324
L1 6 98540357 A T 0.018354 0.0208244 0.018354
L1 6 98431805 G A 0.0153678 -0.0206844 0.0153678
L1 6 98438566 T A 0.0153503 -0.0206835 0.0153503
L1 6 98433708 C A 0.015218 -0.0206766 0.015218
L1 6 98448725 A G 0.0148343 -0.0206564 0.0148343
L1 6 98439152 A T 0.0147238 -0.0206505 0.0147238
L1 6 98489654 T C 0.0145216 -0.0206395 0.0145216
L1 6 98444794 A C 0.0144206 -0.020634 0.0144206
L1 6 98437775 C T 0.0142095 -0.0206223 0.0142095
L1 6 98445008 A C 0.0140166 -0.0206114 0.0140166
L1 6 98398914 C T 0.0140092 -0.020611 0.0140092
L1 6 98431600 T C 0.0139488 -0.0206076 0.0139488
L1 6 98366735 G A 0.0136979 -0.0205932 0.0136979
L1 6 98436938 A G 0.0134924 -0.0205812 0.0134924
L1 6 98394217 C G 0.0131815 -0.0205626 0.0131815
L1 6 98402387 C G 0.0131362 -0.0205599 0.0131362
L1 6 98390677 G T 0.0125465 -0.0205233 0.0125465
L1 6 98448405 A C 0.012271 -0.0205056 0.012271
L1 6 98400834 T C 0.0119244 -0.0204827 0.0119244
L1 6 98390463 A T 0.0119153 -0.0204821 0.0119153
L1 6 98390699 G C 0.0118728 -0.0204792 0.0118728
L1 6 98403406 T C 0.0116734 -0.0204657 0.0116734
L1 6 98388730 T C 0.0113775 -0.0204452 0.0113775
L1 6 98403022 T C 0.0111777 -0.020431 0.0111777
L1 6 98437655 A AC 0.0110013 -0.0204182 0.0110013
L1 6 98434438 T C 0.0108849 -0.0204097 0.0108849
L1 6 98395421 A C 0.0107332 -0.0203985 0.0107332
L1 6 98392312 C T 0.0107145 -0.0203971 0.0107145
L1 6 98398945 G A 0.0107091 -0.0203967 0.0107091
L1 6 98401847 C T 0.0107059 -0.0203964 0.0107059
L1 6 98396176 A G 0.0104524 -0.0203772 0.0104524
L1 6 98399604 C T 0.0104453 -0.0203766 0.0104453
L1 6 98398832 T C 0.0104157 -0.0203744 0.0104157
L1 6 98436333 T A 0.0103084 -0.0203661 0.0103084
L1 6 98401483 C A 0.0102638 -0.0203626 0.0102638
L1 6 98399612 A T 0.0102595 -0.0203622 0.0102595
L1 6 98398843 A AT 0.0102333 -0.0203602 0.0102333
L1 6 98405151 A T 0.0102319 -0.0203601 0.0102319
L1 6 98396351 G A 0.0102315 -0.02036 0.0102315
L1 6 98399407 T C 0.0101212 -0.0203513 0.0101212
L1 6 98405214 G C 0.0100688 -0.0203471 0.0100688
L1 6 98406939 A G 0.00999626 -0.0203413 0.00999626
L1 6 98401808 C T 0.00992673 -0.0203357 0.00992673
L1 6 98403903 C T 0.00971935 -0.0203187 0.00971935
L1 6 98419613 T C 0.00967755 -0.0203153 0.00967755
L1 6 98402211 T G 0.00956356 -0.0203057 0.00956356
L1 6 98412564 C T 0.00952048 -0.0203021 0.00952048
L1 6 98415905 T C 0.0094534 -0.0202964 0.0094534
L1 6 98405337 G C 0.00943448 -0.0202948 0.00943448
L1 6 98402394 C A 0.0092682 -0.0202804 0.0092682
L1 6 98402438 C T 0.00925004 -0.0202788 0.00925004
L1 6 98406850 C T 0.00924196 -0.0202781 0.00924196
L1 6 98397820 T C 0.00909291 -0.020265 0.00909291
L1 6 98404174 C T 0.00906227 -0.0202623 0.00906227
L1 6 98404346 C T 0.00894255 -0.0202515 0.00894255
L1 6 98509711 A G 0.00880315 -0.0202388 0.00880315
L1 6 98423208 A G 0.00866468 -0.020226 0.00866468
L1 6 98418637 C T 0.00823035 -0.0201844 0.00823035
L1 6 98450190 A T 0.00821631 0.020183 0.00821631
L1 6 98416456 T C 0.00812601 -0.020174 0.00812601
L1 6 98415577 G T 0.00808103 -0.0201695 0.00808103
L1 6 98416458 T C 0.00801795 -0.0201632 0.00801795
L1 6 98416581 C A 0.007608 -0.0201205 0.007608
L1 6 98410756 A G 0.00760571 -0.0201203 0.00760571
L1 6 98419195 G A 0.00760371 -0.0201201 0.00760371
L1 6 98416821 C A 0.00731378 -0.0200884 0.00731378
L1 6 98392511 T TTA 0.0072496 -0.0200812 0.0072496
L1 6 98417147 T A 0.00696736 -0.0200489 0.00696736
L1 6 98413299 T C 0.00627609 -0.0199634 0.00627609
L1 6 98426502 G A 0.00616976 -0.0199494 0.00616976
L1 6 98546394 C T 0.00400535 0.0195919 0.00400535
L1 6 98449775 T TATA 0.00368099 0.0195212 0.00368099
L1 6 98517804 T G 0.0028382 -0.019302 0.0028382
L1 6 98522102 A C 0.00282682 -0.0192986 0.00282682
L1 6 98456578 C T 0.00277843 0.019284 0.00277843
L1 6 98476651 G T 0.0027743 0.0192827 0.0027743
L1 6 98452818 CAGTT C 0.00276262 0.0192791 0.00276262
L1 6 98518138 C CCAGGTACTGAAAATAGTACCCA 0.00273086 -0.0192693 0.00273086
L1 6 98517272 A G 0.00267551 -0.0192519 0.00267551
L1 6 98510530 T G 0.00252295 -0.019202 0.00252295
L1 6 98512865 T C 0.00251899 -0.0192006 0.00251899
L1 6 98511568 T C 0.00251038 -0.0191977 0.00251038
L1 6 98502762 A G 0.00250904 -0.0191973 0.00250904
L1 6 98453465 C T 0.0024599 -0.0191804 0.0024599
L1 6 98473185 A G 0.0023793 0.0191519 0.0023793
L1 6 98475160 G A 0.00233744 0.0191368 0.00233744
L1 6 98500715 G A 0.00233372 -0.0191354 0.00233372
L1 6 98457356 A G 0.00227927 0.0191152 0.00227927
L1 6 98486851 G A 0.00224524 -0.0191023 0.00224524
L1 6 98449707 A G 0.00222201 0.0190934 0.00222201
L1 6 98481755 T C 0.00220151 0.0190855 0.00220151
L1 6 98473269 A C 0.00216228 0.0190701 0.00216228
L1 6 98456948 C T 0.00213903 0.0190608 0.00213903

  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. ↩