{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:19:19Z","timestamp":1773933559798,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> Women who carry an <jats:italic>FMR1<\/jats:italic> premutation (PM) can experience two well-established PM-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects ~20\u201330% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects ~6\u201315% carriers); however, emerging evidence indicates that some of these women experience complex health profiles beyond FXPOI and FXTAS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In an effort to better understand predictors for these comorbid conditions, we collected self-reported medical histories on 413 women who carry an <jats:italic>FMR1<\/jats:italic> PM.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> There were 22 health conditions reported by at least 9% of women. In an exploratory analysis, 12 variables were tested in logistic regression models for each comorbid condition, including demographic variables, environmental variables, PM-associated factors, and endorsement of depression and\/or anxiety. More than half of the comorbid conditions studied were associated with women who self-reported having anxiety. Age, smoking, body mass index (BMI), and depression were also significant predictor variables for specific comorbid conditions.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Age, smoking, and BMI were significantly associated with a subset of the comorbid conditions analyzed. Importantly, depression or anxiety were also significantly associated with many of the comorbid health conditions. This work highlights some of the modifiable factors associated with complex health profiles among women with an <jats:italic>FMR1<\/jats:italic> PM.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.715922","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T06:34:13Z","timestamp":1633070053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Predictors of Comorbid Conditions in Women Who Carry an FMR1 Premutation"],"prefix":"10.3389","volume":"12","author":[{"given":"Emily Graves","family":"Allen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Charen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather S.","family":"Hipp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Shubeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashima","family":"Amin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiya","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica Ezzell","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine E.","family":"Shelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie L.","family":"Sherman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/gim.2014.106","article-title":"Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers","volume":"17","author":"Nolin","year":"2015","journal-title":"Genet Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1006\/mgme.2001.3225","article-title":"Fragile X syndrome: a model of gene-brain-behavior relationships","volume":"74","author":"Hagerman","year":"2001","journal-title":"MolGenet Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3389\/fped.2020.00266","article-title":"Fragile X Premutation Associated Conditions (FXPAC)","volume":"8","author":"Johnson","year":"2020","journal-title":"Front Pediatr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/cge.13924","article-title":"Fragile X premutation and associated health conditions: a review","volume":"99","author":"Tassanakijpanich","year":"2021","journal-title":"Clin Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1093\/humrep\/dem148.Epub","article-title":"Examination of reproductive aging milestones among women who carry the FMR1 premutation","volume":"22","author":"Allen","year":"2007","journal-title":"Hum Reprod."},{"key":"B6","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1212\/wnl.57.1.127","article-title":"Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X","volume":"57","author":"Hagerman","year":"2001","journal-title":"Neurology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S1474-4422(13)70125-X","article-title":"Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor\/ataxia syndrome","volume":"12","author":"Hagerman","year":"2013","journal-title":"Lancet Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nrneurol.2016.82","article-title":"Fragile X-associated tremor\/ataxia syndrome - features, mechanisms and management","volume":"12","author":"Hagerman","year":"2016","journal-title":"Nat Rev Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/1096-8628(200023)97:3<189::AID-AJMG1036>3.0.CO;2-J","article-title":"Premature ovarian failure in the fragile X syndrome","volume":"97","author":"Sherman","year":"2000","journal-title":"Am J Med Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/ajmg.a.10862","article-title":"Female carriers of fragile X premutations have no increased risk for additional diseases other than premature ovarian failure","author":"Hundscheid","year":"2003","journal-title":"Am J Med Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/ajmg.a.32060","article-title":"Expanded clinical phenotype of women with the FMR1 premutation","author":"Coffey","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1002\/ajmg.a.35569","article-title":"Immune-mediated disorders among women carriers of fragile X premutation alleles","author":"Winarni","year":"2012","journal-title":"Am J Med Genet A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1866-1955-6-30","article-title":"Associated features in females with an FMR1 premutation","volume":"6","author":"Wheeler","year":"2014","journal-title":"J Neurodev Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"300","DOI":"10.3389\/fgene.2014.00300","article-title":"Health and reproductive experiences of women with an FMR1 premutation with and without fragile X premature ovarian insufficiency","volume":"5","author":"Wheeler","year":"2014","journal-title":"Front Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1002\/ajmg.a.32439","article-title":"Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey","author":"Bailey","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1111\/j.1399-0004.2009.01317.x","article-title":"Co-occurring diagnoses among FMR1 premutation allele carriers","volume":"77","author":"Hunter","year":"2010","journal-title":"Clin Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"564","DOI":"10.3389\/fpsyt.2018.00564","article-title":"Fragile X-Associated Neuropsychiatric Disorders (FXAND)","volume":"9","author":"Hagerman","year":"2018","journal-title":"Front Psychiatry."},{"key":"B18","doi-asserted-by":"publisher","first-page":"eaaw.7195","DOI":"10.1126\/sciadv.aaw7195","article-title":"Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample","volume":"5","author":"Movaghar","year":"2019","journal-title":"Sci Adv"},{"key":"B19","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1352\/0895-8017(2004)109<237:PWACIM>2.0.CO;2","article-title":"Psychological well-being and coping in mothers of youths with autism, Down syndrome, or fragile X syndrome","volume":"109","author":"Abbeduto","year":"2004","journal-title":"Am J Ment Retard."},{"key":"B20","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/ajmg.a.32240","article-title":"Child and genetic variables associated with maternal adaptation to fragile X syndrome: a multidimensional analysis","author":"Bailey","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B21","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s10803-009-0844-y","article-title":"Daily experiences among mothers of adolescents and adults with autism spectrum disorder","volume":"40","author":"Smith","year":"2010","journal-title":"J Autism Dev Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/bf00573637","article-title":"Behavioural phenotypes and family stress in three mental retardation syndromes","volume":"6","author":"Sarimski","year":"1997","journal-title":"Eur Child Adolesc Psychiatry."},{"key":"B23","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1097\/YPG.0b013e3282f97e0b","article-title":"Evidence of depressive symptoms in fragile-X syndrome premutated females","volume":"18","author":"Rodriguez-Revenga","year":"2008","journal-title":"Psychiatr Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/ajmg.b.30786","article-title":"Mood and anxiety disorders in females with the FMR1 premutation","author":"Roberts","year":"2009","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.psyneuen.2011.08.003","article-title":"The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD","volume":"37","author":"Lovell","year":"2012","journal-title":"Psychoneuroendocrinology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.maturitas.2009.08.003","article-title":"Premature menopause or early menopause: long-term health consequences","volume":"65","author":"Shuster","year":"2009","journal-title":"Maturitas."},{"key":"B27","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1055\/s-0033-1356480","article-title":"Biomarkers of ovarian reserve\u2013do they predict somatic aging?","volume":"31","author":"Cedars","year":"2013","journal-title":"Semin Reprod Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/s41436-019-0733-5","article-title":"Clustering of comorbid conditions among women who carry an FMR1 premutation","volume":"22","author":"Allen","year":"2020","journal-title":"Genet Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.5694\/j.1326-5377.2009.tb02471.x","article-title":"Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence","volume":"190","author":"Clarke","year":"2009","journal-title":"Med J Aust."},{"key":"B30","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1365-2788.2006.00896.x","article-title":"Correlates of maternal behaviours in mothers of children with fragile X syndrome","volume":"51","author":"Wheeler","year":"2007","journal-title":"J Intellect Disabil Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.fertnstert.2004.11.059","article-title":"An update: spontaneous premature ovarian failure is not an early menopause","volume":"83","author":"Nelson","year":"2005","journal-title":"Fertil Steril."},{"key":"B32","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/(SICI)1096-8628(19960809)64:2<428::AID-AJMG39>3.0.CO;2-F","article-title":"Survey of the fragile X syndrome and the fragile X E syndrome in a special education needs population","volume":"64","author":"Meadows","year":"1996","journal-title":"Am J Med Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1001\/jama.1993.03510130075034","article-title":"Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test","volume":"270","author":"Brown","year":"1993","journal-title":"JAMA."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/0092-8674(91)90283-5","article-title":"Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox","volume":"67","author":"Fu","year":"1991","journal-title":"Cell."},{"key":"B35","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.ajog.2005.08.047","article-title":"Epidemiology, etiology, and diagnosis of osteoporosis","volume":"194","author":"Lane","year":"2006","journal-title":"Am J Obstet Gynecol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/mds.22838","article-title":"How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor","volume":"25","author":"Louis","year":"2010","journal-title":"Mov Disord."},{"key":"B37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.arr.2016.01.007","article-title":"Hypertension and aging","volume":"26","author":"Buford","year":"2016","journal-title":"Ageing Res Rev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s00508-016-1096-4","article-title":"Gait disorders in adults and the elderly: a clinical guide","volume":"129","author":"Pirker","year":"2017","journal-title":"Wien Klin Wochenschr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.smrv.2016.07.002","article-title":"Prevalence of obstructive sleep apnea in the general population: a systematic review","volume":"34","author":"Senaratna","year":"2017","journal-title":"Sleep Med Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1080\/030097402760375214","article-title":"Relationship between fibromyalgia features and smoking","volume":"31","author":"Yunus","year":"2002","journal-title":"Scand J Rheumatol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.jbspin.2010.07.018","article-title":"Smoking habits influence pain and functional and psychiatric features in fibromyalgia","volume":"78","author":"Lee","year":"2011","journal-title":"Joint Bone Spine."},{"key":"B42","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12971-015-0042-y","article-title":"Prevalence of smoking in adults with chronic pain","volume":"13","author":"Orhurhu","year":"2015","journal-title":"Tob Induc Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"72","DOI":"10.34171\/mjiri.34.72","article-title":"Association of cigarette smoking with irritable bowel syndrome: a cross-sectional study","volume":"34","author":"Mahmood","year":"2020","journal-title":"Med J Islam Repub Iran."},{"key":"B44","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.smrv.2012.08.002","article-title":"Obesity and obstructive sleep apnea\u2013clinical significance of weight loss","volume":"17","author":"Tuomilehto","year":"2013","journal-title":"Sleep Med Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.phrs.2017.05.013","article-title":"Obesity and hypertension","volume":"122","author":"Seravalle","year":"2017","journal-title":"Pharmacol Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/ajmg.b.30482","article-title":"CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor\/ataxia syndrome (FXTAS)","author":"Tassone","year":"2007","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/emboj.2010.21","article-title":"Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients","volume":"29","author":"Sellier","year":"2010","journal-title":"EMBO J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"103","DOI":"10.4161\/rna.1.2.1035","article-title":"FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor\/ataxia syndrome (FXTAS)","volume":"1","author":"Tassone","year":"2004","journal-title":"RNA Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","article-title":"CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome","volume":"78","author":"Todd","year":"2013","journal-title":"Neuron."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.715922\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T06:34:16Z","timestamp":1633070056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.715922\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":49,"alternative-id":["10.3389\/fpsyt.2021.715922"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.715922","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]},"article-number":"715922"}}