Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
06
05
2022
accepted:
29
06
2023
medline:
11
9
2023
pubmed:
8
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study of individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.
Identifiants
pubmed: 37550530
doi: 10.1038/s41588-023-01464-1
pii: 10.1038/s41588-023-01464-1
pmc: PMC10947608
mid: NIHMS1971839
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1462-1470Subventions
Organisme : NIDA NIH HHS
ID : U01 DA041120
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041093
Pays : United States
Organisme : BLRD VA
ID : I01 BX004189
Pays : United States
Organisme : NIDA NIH HHS
ID : U24 DA041123
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067025
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041117
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041148
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125246
Pays : United States
Organisme : NIDA NIH HHS
ID : U24 DA041147
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH116442
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041134
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041022
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH122394
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041156
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041025
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH087004
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041089
Pays : United States
Organisme : BLRD VA
ID : I01 BX002395
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041106
Pays : United States
Organisme : NIMH NIH HHS
ID : L40 MH127664
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH096679
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041028
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041048
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041174
Pays : United States
Organisme : NIMH NIH HHS
ID : K08 MH122911
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
J Clin Psychiatry. 2008 Feb;69(2):266-73
pubmed: 18348600
Pharmacogenomics. 2005 Sep;6(6):639-46
pubmed: 16143003
Int J Eat Disord. 2018 Jun;51(6):518-526
pubmed: 29500865
Science. 2020 Nov 13;370(6518):
pubmed: 33184180
PLoS Genet. 2022 Jul 19;18(7):e1010299
pubmed: 35853082
Neuroimage. 2016 Jan 1;124(Pt B):1115-1119
pubmed: 25840117
Bioinformatics. 2016 Sep 1;32(17):2598-603
pubmed: 27187203
Nature. 2021 Feb;590(7845):290-299
pubmed: 33568819
Nat Biotechnol. 2013 Dec;31(12):1102-10
pubmed: 24270849
Int J Eat Disord. 2009 Dec;42(8):687-705
pubmed: 19621466
Commun Biol. 2021 Feb 3;4(1):156
pubmed: 33536631
BMC Psychiatry. 2020 Jun 16;20(1):307
pubmed: 32546136
Dev Cogn Neurosci. 2018 Aug;32:4-7
pubmed: 29051027
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Int J Eat Disord. 2008 Mar;41(2):174-9
pubmed: 18095307
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Medicine (Baltimore). 2015 Dec;94(52):e2098
pubmed: 26717356
Obes Res. 2002 Oct;10(10):1021-9
pubmed: 12376583
Eur Eat Disord Rev. 2017 Sep;25(5):317-328
pubmed: 28467032
Int J Eat Disord. 2021 May;54(5):785-793
pubmed: 33644868
Nature. 2019 Dec;576(7785):138-142
pubmed: 31748741
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Nat Commun. 2019 Oct 29;10(1):4923
pubmed: 31664021
Int J Eat Disord. 2020 Sep;53(9):1353-1376
pubmed: 32583527
Nat Commun. 2018 Jan 15;9(1):224
pubmed: 29335400
Ann Intern Med. 2016 Sep 20;165(6):409-20
pubmed: 27367316
Eat Behav. 2001 Summer;2(2):105-12
pubmed: 15001040
Biol Psychiatry. 2013 May 1;73(9):904-14
pubmed: 23290497
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Expert Rev Hematol. 2016 Nov;9(11):1075-1080
pubmed: 27701928
Mol Genet Genomic Med. 2013 Sep 1;1(3):131-141
pubmed: 24058921
Transl Psychiatry. 2017 Feb 21;7(2):e1040
pubmed: 28221362
JMIR Med Inform. 2019 Nov 29;7(4):e14325
pubmed: 31553307
Addict Biol. 2017 Jan;22(1):163-171
pubmed: 26419743
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Neuropsychopharmacology. 2021 Jan;46(1):131-142
pubmed: 32541809
Mol Psychiatry. 2020 Aug;25(8):1673-1687
pubmed: 32099098
Womens Health Issues. 2019 Jun 25;29 Suppl 1:S56-S66
pubmed: 31253243
PLoS Genet. 2006 Dec;2(12):e190
pubmed: 17194218
Nat Commun. 2019 Apr 16;10(1):1776
pubmed: 30992449
Am J Clin Nutr. 2010 Jun;91(6):1568-73
pubmed: 20427731
Nat Rev Endocrinol. 2021 Dec;17(12):745-755
pubmed: 34608277
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Am J Hum Genet. 2019 Oct 3;105(4):763-772
pubmed: 31564439
Nat Genet. 2020 Nov;52(11):1158-1168
pubmed: 33106633
Int J Eat Disord. 2003;34 Suppl:S107-16
pubmed: 12900991
J Stroke. 2017 Jan;19(1):3-10
pubmed: 28178408
Bioinformatics. 2022 Jan 3;38(2):536-539
pubmed: 34529038
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
J R Stat Soc Series B Stat Methodol. 2020 Dec;82(5):1273-1300
pubmed: 37220626
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
Nat Neurosci. 2019 Sep;22(9):1394-1401
pubmed: 31358989
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
Eat Behav. 2001 Summer;2(2):183-92
pubmed: 15001045
Int J Eat Disord. 2004 Nov;36(3):307-14
pubmed: 15478129
J Clin Epidemiol. 2016 Feb;70:214-23
pubmed: 26441289
Bioinformatics. 2010 Nov 15;26(22):2867-73
pubmed: 20926424
Nat Neurosci. 2021 Oct;24(10):1367-1376
pubmed: 34446935
Biol Psychiatry. 2018 Sep 1;84(5):345-354
pubmed: 29859631
Dev Cell. 2018 Sep 10;46(5):581-594.e4
pubmed: 30122630
Psychol Med. 2010 Nov;40(11):1899-906
pubmed: 20132584