Context: Functional hypothalamic amenorrhea (HA) is a common, acquired form of hypogonadotropic hypogonadism that occurs in the setting of energy deficits and/or stress. Variability in individual susceptibility to these stressors, HA heritability, and previous identification of several rare sequence variants (RSVs) in genes associated with the rare disorder, isolated hypogonadotropic hypogonadism (IHH), in individuals with HA suggest a possible genetic contribution to HA susceptibility.
Objective: We sought to determine whether the burden of RSVs in IHH-related genes is greater in women with HA than controls.
Design: We compared patients with HA to control women.
Setting: The study was conducted at secondary referral centers.
Patients And Other Participants: Women with HA (n = 106) and control women (ClinSeq study; n = 468).
Interventions: We performed exome sequencing in all patients and controls.
Main Outcome Measure(s): The frequency of RSVs in 53 IHH-associated genes was determined using rare variant burden and association tests.
Results: RSVs were overrepresented in women with HA compared with controls (P = .007). Seventy-eight heterozygous RSVs in 33 genes were identified in 58 women with HA (36.8% of alleles) compared to 255 RSVs in 41 genes among 200 control women (27.2%).
Conclusions: Women with HA are enriched for RSVs in genes that cause IHH, suggesting that variation in genes associated with gonadotropin-releasing hormone neuronal ontogeny and function may be a major determinant of individual susceptibility to developing HA in the face of diet, exercise, and/or stress.
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http://dx.doi.org/10.1210/clinem/dgaa609 | DOI Listing |
J Neuroendocrinol
October 2024
Center for Reproductive Medicine, Reproductive Endocrine Unit and The Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
medRxiv
May 2024
Genomic Medicine Center, Children's Mercy Research Institute and Children's Mercy Kansas City, Kansas City, MO, USA.
Hum Genet
November 2023
Reproductive Endocrine Unit of the Department of Medicine, Harvard Reproductive Endocrine Sciences Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
J Virol Methods
September 2023
Institute of Plant Virology, Fujian Agricultural and Forestry University, Fuzhou 350002, China; State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China. Electronic address:
Geminiviruses are a family of single-stranded DNA viruses that cause significant yield losses in crop production worldwide. Transcription start site (TSS) mapping is crucial in understanding the gene expression mechanisms of geminiviruses. However, this often requires costly and laborious experiments.
View Article and Find Full Text PDFHematol Oncol
October 2023
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Non-follicular low-grade B-cell lymphomas (LGBCL) are biologically diverse entities that share clinical and histologic features that make definitive pathologic categorization challenging. While most patients with LGBCL have an indolent course, some experience aggressive disease, highlighting additional heterogeneity across these subtypes. To investigate the potential for shared biology across subtypes, we performed RNA sequencing and applied machine learning approaches that identified five clusters of patients that grouped independently of subtype.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!