Editing Genetics of chronic fatigue syndrome

The '''genes''' linked to [[myalgic encephalomyelitis]]/[[chronic fatigue syndrome]] is an area of research as [[ME/CFS]] has been observed in families.<ref name="cdc2018">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html | title = Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-11-08 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-02-08}}</ref> It is unknown if there is a genetic link or common environmental exposure (infectious or toxic). Studies of twins show higher rates of ME/CFS in identical than fraternal twins. The [[Centers for Disease Control and Prevention]] (CDC) notes that specific genetic associations have not been established.<ref name="cdc2018" />

=== The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS ===
A new hypothesis, the indolamine-2,3-dioxygenase ([[IDO]]) [[metabolic trap]], was developed and formulated as a mathematical model. The historical occurrence of [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|ME/CFS outbreaks]] is a singular feature of the disease and implies that any predisposing genetic mutation must be common. A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of [[IDO1]] and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation. This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable.<ref name="Kashi2019" />

=== ME/CFS Gene Study ===
The [[ME/CFS Gene Study]] is still collecting data, but the initial pilot study by Perez et al. (2019) found 10 relatively common genes or gene variants were significantly more common in people with ME/CFS.<ref name="Nathanson2019" /> These were [[Cytochrome P450 2D6|CYP2D6]], [[Proline-rich transmembrane protein 4|PRRT4]], [[Serine Protease 56|PRSS56]], [[Armadillo Like Helical Domain Containing 4|C14orf37]], [[Ankyrin Repeat And Death Domain Containing 1B|ANKDD1B]], [[G protein-coupled bile acid receptor 1|GPBAR1]], [[Luteinizing hormone subunit beta|LHB]], [[ADAM metallopeptidase with thrombospondin type 1 motif 19|ADAMTS19]], [[Valyl-tRNA synthetase 2, mitochondrial|VARS2]], and [[Complexin 2|CPLX2]].<ref name="Nathanson2019" />

In 2021 the pilot was reviewed and found to have had serious methodological flaws that rendered its findings incorrect and conclusions spurious.<ref>{{Cite journal | title = Re-analysis of Genetic Risks for Chronic Fatigue Syndrome From 23andMe Data Finds Few Remain | date = 2021-03-18 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012483/|journal=Frontiers in Pediatrics|volume=9|pages=590040 | last =Bedford | first =Felice L. | last2=Greshake Tzovaras | first2 = Bastian|doi=10.3389/fped.2021.590040|pmc=8012483|pmid=33816394|issn=2296-2360}}</ref> It is not clear how a study with such obvious and serious problems might even have passed peer review.

=== Utah Population Database study ===
A 2011 study by Albright et al showed evidence of a heritable contribution to [[chronic fatigue syndrome]] (CFS).<ref>{{Cite journal | title = Evidence for a heritable predisposition to Chronic Fatigue Syndrome | date = 2011-05-27| url = https://pubmed.ncbi.nlm.nih.gov/21619629/|journal=BMC neurology|volume=11| pages=62 | last = Albright | first = Frederick | last2 = Light | first2 = Kathleen | last3 = Light | first3 = Alan | last4 = Bateman | first4 = Lucinda | last5 = Cannon-Albright | first5 = Lisa A.|doi=10.1186/1471-2377-11-62|pmc=3128000|pmid=21619629|issn=1471-2377}}</ref>  Using the extensive records of the Utah Population Database (UPDB), the study "shows clear evidence of significant excess familial clustering and significantly elevated risks for [[Chronic fatigue syndrome|CFS]] among first, second, and third degree relatives of CFS cases. The results strongly support a genetic contribution to predisposition to CFS as it is currently defined and diagnosed by clinicians in Utah." Increased outbreak rates in first degree relatives are not automatically assumed to be genetic because the first degree relatives often share the same lifestyle and environment. However, a significantly increased incidence (95% confidence interval) in second and third degree relatives strongly indicated a genetic contribution to CFS, given the much lower likelihood of these relatives sharing common risks and environments.<ref>{{Cite journal | title = Evidence for a heritable predisposition to Chronic Fatigue Syndrome | date = 2011-05-27| url = https://pubmed.ncbi.nlm.nih.gov/21619629/|journal=BMC neurology|volume=11| pages=62 | last = Albright | first = Frederick | last2 = Light | first2 = Kathleen | last3 = Light | first3 = Alan | last4 = Bateman | first4 = Lucinda | last5 = Cannon-Albright | first5 = Lisa A.|doi=10.1186/1471-2377-11-62|pmc=3128000|pmid=21619629|issn=1471-2377}}</ref> 
[[File:Genetic Relationship graph.png|center|Albright,2011 study]]

=== Family history and twin studies ===
A 2001 study in the [[United Kingdom|UK]] showed "there were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects."<ref name="Walsh2001">{{Cite journal | last = Walsh | first = C.M.  | author-link = | last2 = Zainal | first2 = N. Z. | authorlink2 = | last3 = Middleton | first3 = S.J. | authorlink3 = | last4 = Paykel | first4 = E. S. | authorlink4 = | date = Sep 2001 | title = A family history study of chronic fatigue syndrome | url =https://doi.org/10.1097/00041444-200109000-00003|journal=Psychiatric Genetics|language=en|volume=11|issue=3| pages=123–128|doi=10.1097/00041444-200109000-00003|issn=0955-8829|quote=|via=}}</ref> Three twin studies (one in Australia, one in Washington, US, both in 2001, and one in the UK in 2007) showed that the correlations for prolonged and chronic fatigue were significantly higher in monozygotic than dizygotic twins for each definition of chronic fatigue syndrome.<ref name="Buchwald, 2001" /><ref name="Hickie, 2001" /><ref name="Schur, 2007" />

=== Haplogroups ===
One study showed that patients with [[mitochondrial DNA]] from certain haplogroups correlated with variations in [[gastrointestinal]], [[neurological]], and [[inflammatory]] symptoms.<ref name="Hanson2016" />

===HLA alleles===
[[Human leukocyte antigen genes]] associations were investigated by Lande et al. (2020) because these gene variants are considered hallmarks for [[autoimmune hypothesis|autoimmune]] disease; two HLA associations were found to be more common in ME/CFS patients, but the majority of ME/CFS patients did not have these.<ref name="Lande2020" />

===Other genes ===
[[Glutamate receptor, ionotropic, kinase 2]] (GRIK2) and [[neuronal PAS domain protein 2]] (NPAS2) were also investigated in a CDC by Smith et al. (2011).<ref name="Smith2011" />

A review by Dibble, [[Simon McGrath|McGrath]] and [[Chris Ponting|Ponting]] (2020) in preparation for the [[DecodeME]] study stated that research on the UK Biobank patient data showed associations for [[SLC25A15]] (rs7337312), [[P4HA1]] (rs150954845), [[EBF3]] (rs148723539) and  [[COX7B2]] (rs564809936).<ref name="Dibble2020" />

The largest genetic study of ME/CFS patients was published by Hajdarevic et al. in 2022; and analysed data from over 2,500 patients from the UK Biobank, Norway and Denmark, reported they "did not find any ME/CFS risk loci displaying genome-wide significance". The study did find that the [[tubulin polymerization promoting protein|Tubulin Polymerization Promoting Protein]] (TPPP) region may be implicated in ME/CFS.<ref name="Hajdarevic2022" /><ref name="TPPP">{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TPPP | title = TPPP Gene {{!}} TPPP Protein {{!}} TPPP Antibody | last = | first = | authorlink = | date = | website = GeneCards|archive-url=|archive-date=|url-status=|access-date=2022-03-29}}</ref> TPPP is an antibody expressed in the [[brain]]. Other  genes identified [[LINC00333]], [[RIN3]], [[IGFBP1]]/[[IGFBP3]], [[IZUMO1]]/[[FUT1]] and [[ZBTB46]] but [[Protein tyrosine phosphatase non-receptor type 22|PTPN22]] and [[Cytotoxic T-lymphocyte associated protein 4|CTLA4]] genes reported in previous research did not show significance.<ref name="Hajdarevic2022" /> Hajdarevic and colleagues found more significant associations within the Norwegian cohort, who (like the Danish cohort) were diagnosed using the strict [[Canadian Consensus Criteria]], whereas the majority of data came from UK patient self-reported diagnosis. They commented that statistical significance would need approximately 10 times more patient data, which the [[DecodeME]] project was hoped to provide.<ref name="Hajdarevic2022" />

==Notable studies==
*2001, A twin study of the etiology of prolonged fatigue and immune activation<ref name="Hickie, 2001">{{Cite journal | last = Hickie | first1 = IB | authorlink1 = Ian Hickie | last2 = Bansal | first2 = AS | authorlink2 = Amolak Bansal | last3 = Kirk | first3 = KM | authorlink3 = | last4 = Lloyd | first4 = AR | authorlink4 = Andrew Lloyd | last5 = Martin | first5 = NG | authorlink5 = | title = A twin study of the etiology of prolonged fatigue and immune activation| journal = Twin Research | volume = 4 | issue = 2 | page = 94-102 | date = 2001| doi = 10.1375/1369052012209 | url = https://www.cambridge.org/core/journals/twin-research-and-human-genetics/article/twin-study-of-the-etiology-of-prolonged-fatigue-and-immune-activation/23C27BC6F37EC4D87ED788A9C0EB624C | pmid = 11665341}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/11665341 (Abstract)]
*2001, A twin study of chronic fatigue<ref name="Buchwald, 2001">{{Cite journal | last1 = Buchwald | first1 =D. | authorlink1 = Dedra Buchwald | last2 = Herrell | first2 = R. | authorlink2 = | last3 = Ashton | first3 = S. | authorlink3 = | last4 = Belcourt | first4 = M. | authorlink4 = | last5 = Schmaling | first5 = K. | authorlink5 = | last6 = Sullivan | first6 = P. | authorlink6 = | last7 = Neale | first7 = M. | authorlink7 = | last8 = Goldberg | first8 = J. | author-link8 = | title = A twin study of chronic fatigue.| journal = Psychosomatic Medicine | volume = 63 | issue = 6 | page = 936-943 | date = 2001 | pmid = 11719632 | doi = | url = https://www.ncbi.nlm.nih.gov/pubmed/1171963}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/11719632 (Abstract)]
*2006, Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes<ref name="Goertzel2006">{{Cite journal | last = Goertzel | first = Benjamin N.  | author-link = | last2 = Pennachin | first2 = Cassio | authorlink2 = | last3 = de Souza Coelho | first3 = Lucio | authorlink3 = | last4 = Gurbaxani | first4 = Brian | authorlink4 = | last5 = Maloney | first5 = Elizabeth M. | authorlink5 = Elizabeth M. Maloney | last6 = Jones | first6 = James F. | authorlink6 = James Jones | date = April 2006 | title = Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/16610957|journal=Pharmacogenomics|volume=7|issue=3 | pages = 475–483|doi=10.2217/14622416.7.3.475|issn=1462-2416|pmid=16610957|quote=|via=}}</ref> [[pubmed:16610957|(Full text)]]  <blockquote>Three genes were found to be common in a group of people with Chronic Fatigue Syndrome compared to the general population; [[Tryptophan hydroxylase 2|TPH2]] - neuronal [[tryptophan]] hydroxylase, [[Catechol-O-methyltransferase|COMT]] - catechol-O-methyltransferase, and [[nuclear receptor subfamily 3 group C member 1 glucocorticoid receptor|NR3C1]] - nuclear receptor subfamily 3, group C, member 1 [[glucocorticoid]] receptor, together these three have an accuracy of 76%.<ref name="Goertzel2006" /></blockquote>
*2007, Twin analyses of fatigue<ref name="Schur, 2007">{{Cite journal | last1 = Schur | first1 = Ellen | authorlink1 = | last2 = Afari | first2 = Niloofar | authorlink2 = | last3 = Goldberg | first3 = Jack | authorlink3 = | last4 = Buchwald | first4 = Dedra | authorlink4 = Dedra Buchwald | last5 = Sullivan | first5 = Patrick F. | authorlink5 = | title = Twin analyses of fatigue | journal = Twin Research and Human Genetics | volume = 10 | issue = 5 | page = 729-733 | date = 2007 | doi =  10.1375/twin.10.5.729 }}</ref>
*2009, A gene signature for post-Infectious chronic fatigue syndrome<ref name="Chaudhuri2009">{{Cite journal | title = A gene signature for post-infectious chronic fatigue syndrome | date = 2009-06-25| url = https://doi.org/10.1186/1755-8794-2-38|journal=BMC Medical Genomics|volume=2|issue=1 | pages = 38 | last = Gow | first = John W.  | author-link = | last2 = Hagan | first2 = Suzanne | authorlink2 = | last3 = Herzyk | first3 = Pawel | authorlink3 = | last4 = Cannon | first4 = Celia | authorlink4 = | last5 = Behan | first5 = Peter O. | authorlink5 = Peter Behan | last6 = Chaudhuri | first6 = Abhijit | authorlink6 = Abhijit Chaudhuri | last8 = | first8 =   |doi=10.1186/1755-8794-2-38|pmc=|pmid=|access-date=|issn=1755-8794|quote=|via=}}</ref> [https://bmcmedgenomics.biomedcentral.com/articles/10.1186/1755-8794-2-38 (Full Text)]
*2009, Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects<ref name="Light2009">{{Cite journal | last1 = Light | first1 = A.R. | authorlink =  Alan Light | last2 = White | first2 = A.T. | authorlink2 = Andrea White | last3 = Hughen | first3 =R.W. | last4 = Light | first4 = K.C. | authorlink4 =  Kathleen Light | date = 2009 | title =  Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects | journal = The Journal of Pain | volume = 10 | pages = 1099-1112 | pmc = PMC2757484 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/}}</ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/ (Full Text)]
*2011, Evidence for a heritable predisposition to Chronic Fatigue Syndrome<ref name="Albright, 2011">{{Cite journal | last1 = Albright | first1 = Frederick | authorlink1 = Frederick Albright | last2 = Light | first2 = Kathleen | authorlink2 = Kathleen Light | last3 = Light | first3 = Alan | authorlink3 = Alan Light | last4 = Bateman | first4 = Lucinda | authorlink4 = Lucinda Bateman | last5 = Cannon-Albright | first5 = Lisa A | authorlink5 = Lisa Cannon-Albright| title = Evidence for a heritable predisposition to Chronic Fatigue Syndrome |url = https://doi.org/10.1111/j.1365-2796.2011.02405.x| journal = BMC Neurology | volume = 11 | issue = 62 | page = | date = 2011| doi = 10.1186/1471-2377-11-62}}</ref> [http://dx.doi.org/10.1186/1471-2377-11-62 (Abstract)]
*2011, Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome<ref name="Light2011a">{{Cite journal | last = Light | first = A.R.  | author-link = Alan Light | last2 = Bateman | first2 = L. | authorlink2 = Lucinda Bateman | last3 = Jo | first3 =D. | authorlink3 = Daehyun Jo | last4 = Hughen | first4 = R. W. | authorlink4 = Ronald Hughen | last5 = VanHaitsma | first5 = T. A. | authorlink5 = Timothy Vanhaitsma | last6 = White | first6 = A. T. | authorlink6 = Andrea White | last7 = Light | first7 = K. C. | authorlink7 = Kathleen Light | date = 2011-07-13 | title = Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome | url =https://doi.org/10.1111/j.1365-2796.2011.02405.x|journal=Journal of Internal Medicine|language=en|volume=271|issue=1| pages=64–81|doi=10.1111/j.1365-2796.2011.02405.x|issn=0954-6820|pmc=3175315|pmid=21615807|quote=|via=}}</ref> [https://doi.org/10.1111/j.1365-2796.2011.02405.x (Full text)]
*2011, Convergent Genomic Studies Identify Association of GRIK2 and NPAS2 with Chronic Fatigue Syndrome<ref name="Smith2011">{{Cite journal | title = Convergent Genomic Studies Identify Association of GRIK2 and NPAS2 with Chronic Fatigue Syndrome | date = 2011 | url=https://www.karger.com/Article/FullText/326692|journal=Neuropsychobiology|volume=64|issue=4| pages=183–194 | last = Smith | first = Alicia K.  | author-link = | last2 = Fang | first2 = Hong | authorlink2 = | last3 = Whistler | first3 = Toni | authorlink3 = | last4 = Unger | first4 = Elizabeth R. | author-link4 =  Elizabeth Unger | last5 = Rajeevan | first5 = Mangalathu S. | authorlink5 = |language=english|doi=10.1159/000326692|pmc=PMC3701888|pmid=21912186|access-date=|issn=0302-282X|quote=|via=}}</ref> [https://doi.org/10.1159/000326692 (Full text)]
*2016, Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome<ref name="Schlauch, 2016">{{Cite journal | last1 = Schlauch | first1 = Karen A. | authorlink1 = Karen Schlauch | last2 = Khaiboullina | first2 = Svetlana F. | authorlink2 = Svetlana Khaiboullina | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny de Meirleir | last4 = Rawat | first4 = Shanti | authorlink4 = Shanti Rawat | last5 = Petereit | first5 = J | authorlink5 = | last6 = Rizvanov | first6 = Albert A | authorlink6 = Albert Rizvanov | last7 = Blatt | first7 = Nataliya| authorlink7 = Nataliya Blatt | last8 = Mijatovic | first8 = Tatjana | author-link8 = Tatjana Mijatovic| last9 = Kulick | first9 = D | author-link9 = | last10 = Palotás | first10 = András | authorlink10 = András Palotás | last11 = Lombardi | first11 = Vincent C. | authorlink11 = Vincent Lombardi | title = Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome| journal = Translational Psychiatry | volume = 6 | issue = 2 | page = e730| date = 2016| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872418/ | pmid = | pmc = PMC4872418 | doi = 10.1038/tp.2015.208}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872418/ (Full Text)]
*2016, Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome <ref name="Hanson2016">{{Cite journal | last = Billing-Ross | first = Paul | authorlink = Paul Billing-Ross | last2 = Germain | first2 = Arnaud | authorlink2 = Arnaud Germain | last3 = Ye | first3 = Kaixiong | authorlink3 = Kaixiong Ye | last4 = Keinan | first4 = Alon | authorlink4 = Alon Keinan | last5 = Gu | first5 = Zhenglong | authorlink5 = Zhenglong Gu | last6 = Hanson | first6 = Maureen R. | authorlink6 = Maureen Hanson | date = 2016-01-20 | title = Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome | url =https://doi.org/10.1186/s12967-016-0771-6|journal=Journal of Translational Medicine|volume=14|issue=1| pages=19|doi=10.1186/s12967-016-0771-6|issn=1479-5876|quote=|via=}}</ref> [http://www.translational-medicine.com/content/14/1/19 (Abstract)]
*2018, Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns<ref name="Trivedi2018">{{Cite journal | last = Trivedi | first = Malav S.  | author-link = Malav Trivedi | last2 = Oltra | first2 = Elisa | authorlink2 = Elisa Oltra | last3 = Sarria | first3 = Leonor | authorlink3 = Leonor Sarria | last4 = Rose | first4 = Natasha | authorlink4 = Natasha Rose | last5 = Beljanski | first5 = Vladimir | authorlink5 = Vladimir Beljanski | last6 = Fletcher | first6 = Mary Ann | authorlink6 = Mary Ann Fletcher | last7 = Klimas | first7 = Nancy G. | authorlink7 = Nancy Klimas | last8 = Nathanson | first8 = Lubov | author-link8 = Lubov Nathanson | date = 2018 | title = Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns| url = https://www.ncbi.nlm.nih.gov/pubmed/30036399|journal=PloS One|volume=13|issue=7| pages = e0201066|doi=10.1371/journal.pone.0201066|issn=1932-6203|pmc=|pmid=30036399|quote=|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/30036399 (Abstract)]
*2018, Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.<ref name="Herrera2018">{{Cite journal | last = Herrera | first = Santiago | author-link = Santiago Herrera | last2 = de Vega | first2 = Wilfred C. | authorlink2 = Wilfred de Vega | last3 = Ashbrook | first3 = David | authorlink3 = David Ashbrook | last4 = Vernon | first4 = SuzanneD. | authorlink4 = Suzanne Vernon | last5 = McGowan | first5 = Patrick O. | authorlink5 = Patrick McGowan | date = 2018-12-05 | title = Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/30516085|journal=Epigenetics|volume=|issue=| pages=1–17|doi=10.1080/15592294.2018.1549769|issn=1559-2308|pmid=30516085|quote=|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/30516085 (Abstract)]
*2019, Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome.<ref name="Nguyen2019">{{Cite journal | last = Nguyen | first = Chinh Bkrong | authorlink = Chinh Bkrong Nguyen | last2 = Kumar | first2 = Surendra | authorlink2 = Surendra Kumar | last3 = Zucknick | first3 = Manuela | authorlink3 = Manuela Zucknick | last4 = Kristensen | first4 = Vessela N. | authorlink4 = Vessela Kirstensen | last5 = Gjerstad | first5 = Johannes | authorlink5 = Johannes Gjerstad | last6 = Nilsen | first6 = Hilde | authorlink6 = Nilsen Hilde | last7 = Wyller | first7 = Vegard Bruun | authorlink7 = Vegard Bruun Wyller | date = Feb 2019 | title = Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome | url =https://www.ncbi.nlm.nih.gov/pubmed/30419269|journal=Brain, Behavior, and Immunity|volume=76|issue=| pages=82–96|doi=10.1016/j.bbi.2018.11.008|issn=1090-2139|pmid=30419269|quote=|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/30419269/ (Abstract)]
* 2019, Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study<ref name="Nathanson2019">{{Cite journal | last = Nathanson | first = Lubov | authorlink = Lubov Nathanson | authorlink2 = Travis Craddock | last2 = Craddock | first2 = Travis J.A. | last3 = Klimas | first3 = Nancy G. | authorlink3 = Nancy Klimas | authorlink4 = | last4 = Gemayel | first4 = Kristina | last5 = Del Alamo | first5 = Ana | authorlink5 = Ana Del Alamo | authorlink6 = | last6 = Hilton | first6 = Kelly | last7 = Jaundoo | first7 = Rajeev | authorlink7 = | last8 = Perez | first8 = Melanie | author-link8 = | date = 2019 | title=Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study| url = https://www.frontiersin.org/articles/10.3389/fped.2019.00206/full|journal=Frontiers in Pediatrics|language=English|volume=7|issue= | pages = 206|doi=10.3389/fped.2019.00206|issn=2296-2360}}</ref> [https://doi.org/10.3389/fped.2019.00206 (Full text)]
* 2019, The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS<ref name="Kashi2019">{{Cite journal | last = Kashi | first = Alex A.  | author-link = Alex Kashi | last2 = Davis | first2 = Ronald W. | authorlink2 = Ronald Davis | last3 = Phair | first3 = RobertD. | authorlink3 = Robert Phair | date = Sep 2019 | title = The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS| url = https://www.mdpi.com/2075-4418/9/3/82|journal=Diagnostics|language=en|volume=9|issue=3| pages=82|doi=10.3390/diagnostics9030082|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/3/82/htm (Full text)]
*2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="Lande2020">{{Cite journal | last = Lande | first = Asgeir  | author-link = Asgeir Lande | last2 = Fluge | first2 = Øystein | authorlink2 = Øystein Fluge | last3 = Strand | first3 = Elin B. | authorlink3 = Elin Strand | last4 = Flåm | first4 = Siri T. | authorlink4 = Siri Flåm | last5 = Sosa | first5 = DaysiD. | authorlink5 = Daysi Sosa | last6 = Mella | first6 = Olav | authorlink6 = Olav Mella | last7 = Egeland | first7 = Torstein | authorlink7 = | last8 = Saugstad | first8 = OlaD. | author-link8 = | last9 = Lie | first9 = Benedicte A. | author-link9 = | date = 2020-03-24 | title = Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| url = https://www.nature.com/articles/s41598-020-62157-x|journal=Scientific Reports|language=en|volume=10|issue=1| pages=1–8|doi=10.1038/s41598-020-62157-x|issn=2045-2322|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-020-62157-x (Full text)]
*2020, Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender‐specific changes in the microRNA expression profiling in ME/CFS<ref name="Cheema2020">{{Cite journal | last = Cheema | first = Amanpreet K.  | author-link = | last2 = Sarria | first2 = Leonor | authorlink2 = | last3 = Bekheit | first3 = Mina | authorlink3 = | last4 = Collado | first4 = Fanny | authorlink4 = Fanny Collado | last5 = Almenar‐Pérez | first5 = Eloy | authorlink5 = | last6 = Martín‐Martínez | first6 = Eva | authorlink6 = | last7 = Alegre | first7 = Jose | authorlink7 = José Alegre | last8 = Castro‐Marrero | first8 = Jesus | author-link8 = Jesús Castro-Marrero | last9 = Fletcher | first9 = Mary A. | author-link9 = Mary Ann Fletcher | date = Apr 14, 2020 | title = Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS| url = https://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.15260|journal=Journal of Cellular and Molecular Medicine|language=en|volume=00|issue=| pages=1-13|doi=10.1111/jcmm.15260|issn=1582-4934|pmc=|pmid=32291908|access-date=|quote=|via= | last10 = Klimas | first10 = Nancy | authorlink10 = Nancy Klimas | last11 = Oltra | first11 = Elisa | authorlink11 = Elisa Oltra | last12 = Nathanson | first12 = Lubov | authorlink12 = Lubov Nathanson}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15260 (Full text)]
* 2020, Genetic risk factors of ME/CFS: a critical review<ref name="Dibble2020">{{Cite journal | title = Genetic risk factors of ME/CFS: a critical review | date = 2020-08-03| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530519/|journal=Human Molecular Genetics|volume=29|issue=R1| pages=R117–R124 | last = Dibble | first = Joshua J | author-link = | last2 = McGrath | first2 = Simon J | authorlink2 = Simon McGrath | last3 = Ponting | first3 = Chris P | authorlink3 = Chris Ponting|doi=10.1093/hmg/ddaa169|pmc=7530519|pmid=32744306|access-date=|issn=0964-6906|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530519 (Full text)]
*2021, Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study<ref name="Guerra2021">{{Cite journal | title = Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study | date = Jul 2021| url = https://www.mdpi.com/2218-273X/11/7/961|journal=Biomolecules|volume=11|issue=7| pages=961 | last = Fernandez-Guerra | first = Paula  | author-link = | last2 = Gonzalez-Ebsen | first2 = Ana C. | authorlink2 = | last3 = Boonen | first3 = Susanne E. | authorlink3 = | last4 = Courraud | first4 = Julie | authorlink4 = | last5 = Gregersen | first5 = Niels | authorlink5 = | last6 = Mehlsen | first6 = Jesper | authorlink6 = | last7 = Palmfeldt | first7 = Johan | last8 = Olsen | first8 = Rikke K.J. | last9 = Brinth | first9 = Louise Schouborg|language=en|doi=10.3390/biom11070961|pmc=|pmid=|access-date=|issn=2218-273X|quote=|via=}}</ref> - [https://www.mdpi.com/2218-273X/11/7/961/htm (Full text)]
*2021, Re-analysis of Genetic Risks for Chronic Fatigue Syndrome From 23andMe Data Finds Few Remain<ref>{{Cite journal | title = Re-analysis of Genetic Risks for Chronic Fatigue Syndrome From 23andMe Data Finds Few Remain | date = 2021-03-18 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012483/|journal=Frontiers in Pediatrics|volume=9|pages=590040 | last =Bedford | first =Felice L. | last2=Greshake Tzovaras | first2 = Bastian|doi=10.3389/fped.2021.590040|pmc=8012483|pmid=33816394|issn=2296-2360}}</ref>
*
*2022, Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci<ref name="Hajdarevic2022">{{Cite journal | title = Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci | date = 2022-05-01| url = https://www.sciencedirect.com/science/article/pii/S0889159122000782|journal=Brain, Behavior, and Immunity|volume=102|issue= | pages = 362–369 | last = Hajdarevic | first = Riad | authorlink = Riad Hajdarevic | last2 = Lande | first2 = Asgeir | authorlink2 = Asgeir Lande | last3 = Mehlsen | first3 = Jesper | authorlink3 = | last4 = Rydland | first4 = Anne | authorlink4 = | last5 = Sosa | first5 = DaisyD. | authorlink5 = | last6 = Strand | first6 = Elin B. | authorlink6 = Elin Strand | last7 = Mella | first7 = Olav | authorlink7 = Olav Mella | last8 = Pociot | first8 = Flemming | last9 = Fluge | first9 = Øystein | author-link9 = Øystein Fluge | last10 = Lie | first10 = Benedicte A. | last11 = Viken | first11 = Marte K.|language=en|doi=10.1016/j.bbi.2022.03.010|pmc=|pmid=|access-date=|issn=0889-1591|quote=|via=}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0889159122000782 (Full text)]

==Media Coverage==
*2016, [http://www.meresearch.org.uk/news/genome-wide-associations/ Genome-wide associations]
*2016, [https://cfsremission.wordpress.com/2016/01/23/new-study-found-snps-for-some-symptoms/ New study found SNPs for some symptoms] ([[CFS Remission]], January 23)

==See also==

*[[:Category:Genes|Genes (category)]]
*[[Gene expression]]
*[[ME/CFS Gene Study]]
*[[Genetic testing]]
*[[Mitochondrion]]
== Learn more ==
*[http://hansonlab.org/research/cfs_me/mitochondria/ Mitochondrial DNA and ME/CFS - A Guide to the Hanson Lab's] - 2016 JTM Publication
*[https://solvecfs.org/the-ido-metabolic-trap-hypothesis-for-me-cfs/ The IDO Metabolic Trap Hypothesis For ME/CFS] - Jul 30, 2019 [[Solve ME/CFS Initiative|Solve M.E.]]
*[https://www.youtube.com/watch?v=rtVtH-cwhBY Dr. Ron Davis Gives an Update on ME/CFS Research]- Sep 26, 2019 [[Open Medicine Foundation]] (Gene Mutation Found) 
==References==
{{Reflist}}

[[Category:Triggers and risk factors]]
[[Category:Genetics]]