About

Corrine K. Welt, MD, is a professor in the Department of Internal Medicine with a focus on Endocrinology & Metabolism at the University of Utah. Her work concentrates on disorders of reproduction and their medical consequences, including conditions such as polycystic ovary syndrome, hypothalamic amenorrhea, and early menopause. Her research aims to identify markers and genetic risk factors to facilitate early diagnosis and intervention, thereby helping to alleviate infertility and prevent associated medical issues such as diabetes, high blood pressure, insulin resistance, and high cholesterol. Dr. Welt's background includes extensive training in biochemistry and medicine, with her education spanning the University of Wisconsin–Madison, Cornell University Medical College, and specialized fellowships at Massachusetts General Hospital and other institutions. She is board-certified in Endocrinology, Diabetes & Metabolism and has contributed to numerous publications in her field.

Research topics

• Internal medicine
• Biology
• Medicine
• Endocrinology
• Genetics
• Intensive care medicine
• Bioinformatics
• Dermatology
• Computational biology

Selected publications

• Pathogenic variation in insulin resistance genes is common in polycystic ovary syndrome (PCOS): a strategy for causal gene discovery using whole-exome sequencing (WES) in complex traits

  medRxiv · 2025-08-15

  preprintOpen access

  Abstract Polycystic ovary syndrome (PCOS) is a complex, multi-system, heritable endocrinopathy that is a common cause of anovulatory infertility in reproductive-aged women. While insulin resistance (IR) is not a diagnostic feature, it is widespread in women with PCOS, and often more severe than in women of similar age and BMI. Conversely, women with rare Mendelian disorders of IR also present with features of PCOS. We hypothesize that PCOS is driven by underlying IR, which can be evaluated through a genetic approach. We curated and stratified 310 genes related to three mechanisms of IR using molecular and clinical criteria. We evaluated protein-altering genetic variation in 102 insulin signaling genes, 29 obesity genes, and 22 dyslipidemia genes from whole-exome sequencing data from 675 PCOS patients. 40 insulin signaling genes, 12 obesity genes, and 10 dyslipidemia genes were significantly enriched for protein-altering variation in PCOS cases compared to healthy population controls. Variants in these 62 significantly enriched genes affected 51% of PCOS cases in our study cohort. The 15 highest ranked genes were selected for follow-up: LMNA, LEPR, KCNJ11, BSCL2, ACACA, NTRK2, GCK, ABCC8, SLC2A2, POMC, MC4R, TBC1D4, INSR, NR0B2, and GCKR . 50% of variants identified in these 15 genes were pathogenic, 35% were likely pathogenic, and only 15% were variants of uncertain significance. These findings support IR as a central pathway in PCOS. Furthermore, this study demonstrates that a candidate pathway approach with sufficient pre-processing can successfully identify functionally relevant variants and genes underlying complex traits.

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• Hypogonadism is associated with worse outcomes in arthroscopic rotator cuff repair

  JSES International · 2025-06-05 · 1 citations

  articleOpen access

  <h3>Introduction</h3> The purpose of this pilot study was to determine the association between systemic circulating factor abnormalities known to associate with fracture non-union and outcomes after rotator cuff repair (RCR). <h3>Methods</h3> This was a prospective study of patients undergoing RCR. Preoperatively and at six months postoperatively, we collected patient-reported outcomes (PROs) including visual analogue scale for pain (VAS pain) scores, Simple Shoulder Test (SST) scores, American Shoulder and Elbow Surgeons (ASES) scores, and a magnetic resonance imaging (MRI) scan. Preoperatively, we also collected a battery of serum hormone, vitamin, and metabolic tests including testosterone, estradiol, thyroid-stimulating hormone, luteinizing hormone, vitamin D, calcium, alkaline phosphatase, hemoglobin A1C, and a lipid panel. In men, we collected the Androgen Deficiency in the Aging Male (ADAM) score and, in women, we collected the Menopause Rating Scale (MRS) and these scores were defined as normal or abnormal based upon previously published norms. <h3>Results</h3> Of the 50 included patients, 46/50 (92%) had clinical and 41/50 (82%) had MRI follow-up at six months. 43% (19/44) of included patients were hypogonadal, 32% (12/38) had hypovitaminosis D, 66% (29/44) had dyslipidemia, and 37% (17/46) were diabetic or pre-diabetic. 100% were euthyroid, normocalcemic, and had normal alkaline phosphatase. Hypogonadism was associated with significantly worse VAS pain (2.5±2.2 vs. 1.0±1.1, p=0.014), SST (10±30 vs. 11±20, p=0.037), and ASES (74±19 vs. 88±11, p=0.006) scores postoperatively. While not significant (p=0.102), hypogonadism was associated with lower healing rates (36% vs. 63%). Hypovitaminosis D, diabetes, and dyslipidemia did not associate with clinical outcomes. Dyslipidemia was associated with significantly higher healing rates (71% vs. 31%, p=0.036). <h3>Conclusion</h3> While almost all patients undergoing RCR suffered from systemic biologic deficiencies, only hypogonadism was associated with significant differences in patient-reported outcomes. Given that this factor is modifiable, this result supports larger studies with longer follow-up and exploration of hormone replacement therapy. <h3>Level of evidence</h3> Level II; Prospective Cohort Comparison; Prognosis Study

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• SAT-158 Azoospermia/Oligozoospermia and Prostate Cancer are Increased in Families of Women with Primary Ovarian Insufficiency

  Journal of the Endocrine Society · 2025-10-01

  articleOpen accessSenior author

  Abstract Disclosure: K. Allen-Brady: None. S. Kodoma: None. L.E. Verrilli: None. J.M. Ransay: None. E.B. Johnstone: None. J.J. Horns: None. B.R. Emery: None. L. Cannon-Albright: None. K.I. Aston: None. J.M. Hotaling: None. C.K. Welt: None. Background: Nonobstructive azoospermia (NOA) and primary ovarian insufficiency (POI) have common genetics that may also predispose to cancer risk. Objectives: We hypothesized that NOA or severe oligozoospermia and risk of male cancers would be higher in families of women with POI. Methods: Women with POI were identified using International Classification of Disease codes in electronic medical records (1995-2021) from two major healthcare systems in Utah and reviewed for accuracy. Using genealogy information in the Utah Population Database, women with POI (n=392) and their relatives were included if there were at least three generations of ancestors available. Men with NOA or severe oligozoospermia (≤5 million/mL) from the Subfertility Health and Assisted Reproduction and the Environment Study were identified in these families and risk was calculated in relatives compared to population rates. The relative risk of prostate and testicular cancer was examined using the Utah Cancer Registry. Results: There was an increased risk of NOA/severe oligozoospermia in relatives of women with POI among first- (RR 2.8 [95% CI 1.1, 6.7]; p=0.03), second- (3.1 [1.1, 6.7]; p=0.02), and third-degree relatives (1.8 [1.1, 3.1]; p=0.03). There was evidence for an X chromosome translocation, an autosome inversion and autoimmune polyglandular syndrome as a cause for POI and NOA in three families. In the families with POI and NOA/oligozoospermia (n=21), prostate cancer risk was higher in first- (3.5 [1.1, 8.1]; p=0.016) and second-degree relatives (3.1 [1.9, 4.8]; p=0.000008). Conclusions: The data demonstrate excess familial clustering of severe spermatogenic impairment compared to matched population rates, along with higher prostate cancer risk in relatives of women with POI. These findings support a common genetic contribution to POI, spermatogenic impairment and prostate cancer. Presentation: Saturday, July 12, 2025

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• Azoospermia/Oligozoospermia and Prostate Cancer are Increased in Families of Women with Primary Ovarian Insufficiency

  Journal of the Endocrine Society · 2025-02-22

  articleOpen accessSenior author

  Abstract Background Nonobstructive azoospermia (NOA) and primary ovarian insufficiency (POI) have common genetics that may also predispose to cancer risk. Objectives We hypothesized that NOA or severe oligozoospermia and risk of male cancers would be higher in families of women with POI. Methods Women with POI were identified using International Classification of Disease codes in electronic medical records (1995-2021) from two major healthcare systems in Utah and reviewed for accuracy. Using genealogy information in the Utah Population Database, women with POI (n=392) and their relatives were included if there were at least three generations of ancestors available. Men with NOA or severe oligozoospermia (≤5 million/mL) from the Subfertility Health and Assisted Reproduction and the Environment Study were identified in these families and risk was calculated in relatives compared to population rates. The relative risk of prostate and testicular cancer was examined using the Utah Cancer Registry. Results There was an increased risk of NOA/severe oligozoospermia in relatives of women with POI among first- (RR 2.8 [95% CI 1.1, 6.7]; p=0.03), second- (3.1 [1.1, 6.7]; p=0.02), and third-degree relatives (1.8 [1.1, 3.1]; p=0.03). In these families with POI and NOA/oligozoospermia (n=21), prostate cancer risk was higher in first- (3.5 [1.1, 8.1]; p=0.016) and second-degree relatives (3.1 [1.9, 4.8]; p=0.000008). Conclusions The data demonstrate excess familial clustering of severe spermatogenic impairment compared to matched population rates, along with higher prostate cancer risk in relatives of women with POI. These findings support a common genetic contribution to POI, spermatogenic impairment and prostate cancer.

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• Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-23 · 2 citations

  preprintOpen access

  Abstract Activin-class ligands of the transforming growth factor β family induce follicle-stimulating hormone (FSH) production by pituitary gonadotrope cells in mice via the actions of the transcription factors SMAD3, SMAD4, and FOXL2, which bind to cis -elements in the FSHβ subunit ( Fshb ) promoter. An enhancer region for murine Fshb transcription was identified in vitro . However, deletion of the region using CRISPR-Cas9 did not affect FSH synthesis or secretion in mice. Using single-nucleus ATAC-seq of whole murine pituitaries, we identified three additional open chromatin regions upstream of Fshb exclusively in gonadotropes. These regions, as well as the Fshb gene, were fully or partially closed in gonadotropes of FSH-deficient mice with genetically or pharmacologically inactivated activin type II receptors. The initially characterized enhancer region did not significantly alter basal or activin-stimulated murine Fshb promoter-reporter activity in homologous LβT2 cells. In contrast, the other three open chromatin regions enhanced basal and activin A-stimulated Fshb promoter-reporter activity in LβT2 cells, with the two most distal showing the greatest effects. These two regions were open, exhibited enrichment of the enhancer mark H3K27ac, and were bound by SMAD2/3 and FOXL2 in response to activin A in LβT2 cells. The most distal enhancer exhibited strong FOXL2 and weak SMAD4 binding in gel shift assays. SMAD4, but not FOXL2, directly bound the other distal enhancer. Mutation of defined FOXL2 and SMAD4 cis -elements diminished enhancer activity in reporter assays in LβT2 cells. Collectively, the data indicate that there may be as many as four activin-sensitive enhancers upstream of murine Fshb .

  PublisherDOI

• Heterozygous <i>Eif4nif1</i> Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women

  Endocrinology · 2025-01-17 · 1 citations

  articleOpen accessSenior author

  We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The Eif4enif1 C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.1286C>G stop-gain mutation in exon 10. The hybrid offspring of CMV-Cre mice with Eif4enif1WT/flx mice were designated Eif4enif1WT/Δ for simplicity. A subset of female heterozygotes (Eif4enif1WT/Δ) had no litters. In those with litters, the final litter was earlier (5.4 ± 2.6 vs 10.5 ± 0.7 months; P = .02). Heterozygous breeding pair (Eif4enif1WT/Δ × Eif4enif1WT/Δ) litter size was 60% of WT litter size (3.9 ± 2.0 vs 6.5 ± 3.0 pups/litter; P < .001). The genotypes were 35% Eif4enif1WT/flx and 65% Eif4enif1WT/Δ, with no homozygotes. Homozygote embryos did not develop beyond the 4- to 8-cell stage. The number of follicles in ovaries from Eif4enif1WT/Δ mice was lower starting at the primordial (499 ± 290 vs 1445 ± 381) and primary follicle stage (1069 ± 346 vs 1450 ± 193) on day 10 (P < .05). The preantral follicle number was lower starting on day 21 (213 ± 86 vs 522 ± 227; P < .01). Examination of ribosome protected mRNAs demonstrated altered mRNA expression. The Eif4enif1 stop-gain mice replicate the POI phenotype in women based on an earlier end to reproduction due to oocyte loss. The unique mouse model provides a platform to study regulation of protein translation across oocyte and embryo development in mammals.

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• Acceptability of biologic treatments to patients undergoing rotator cuff repair

  JSES Reviews Reports and Techniques · 2025-03-09

  articleOpen access

  Background: The objective of this study was to determine the acceptability of biologic treatments for patients undergoing rotator cuff repair. Methods: This is a survey-based analysis of treatment acceptability of patients undergoing rotator cuff repair. Preoperatively, we collected demographics and survey responses. Patients were surveyed using a 5-point Likert scale regarding their willingness to undergo variations on biologic treatments for rotator cuff tears. These variations included frequency of treatment (daily, every other day, and weekly); duration of treatment (1, 3, and 6 months); side effect frequency (10%, 25%, 50%, and 75%); efficacy in terms of increased success rates (10% more, 20% more, and 30% more); and method of administration (injection, oral, and implantable). Descriptive statistical analysis was performed. Results: Fifty-five patients responded to the survey. The cohort was 65% male, with a mean ± standard deviation age of 60 ± 11 years, body mass index of 30 ± 7, and Charlson comorbidity index of 2 ± 1. With regards to frequency of treatment, 73% of patients either strongly agreed or agreed that they were willing to take a pill daily if it would increase the likelihood of success. For injections, 80% of patients either strongly agreed or agreed that they were willing to undergo an injection once, 71% weekly, 76% monthly, and 76% every 3 months. With regards to duration, 76% either strongly agreed or agreed that they were willing to take a medication for 1 month, 64% for 3 months, and 55% for 6 months. With regards to side effects, 47% either strongly agreed or agreed that they were willing to undergo a treatment with 10% side effects, 13% with 25% side effects, 7% with 50% side effects, and 7% with 75% side effects. With regards to efficacy, 73% either strongly agreed or agreed that they were willing to undergo a biologic treatment if it increased their success rates by even 10%. Conclusion: Based upon these survey responses, the biologic treatment options most acceptable to patients would be a pill or injection, administered for up to 3 months after surgery, with fewer than 10% of patients experiencing side effects. Most patients were willing to undergo a biologic treatment even if it only increased their likelihood of success by 10%. Therefore, based on these results, researchers and physicians developing biologic treatments could focus on avenues that only slightly increase success rates and can be administered within 3 months of surgery provided there is a favorable side effect profile.

  PublisherDOI

• Worth the Effort: Lessons for Discovery and Care From an Unusual Case of Gorlin Syndrome

  American Journal of Medical Genetics Part A · 2025-05-03

  articleOpen access

  Gorlin-Goltz Syndrome (GGS) is a rare autosomal dominant genetic disorder encompassing a diverse range of clinical manifestations, including congenital anomalies and predisposition to cancer. Pathogenic variants in PTCH1 and SUFU account for up to 79% and 6% of cases, respectively. Currently, an estimated 15%-27% of individuals with a clinical diagnosis of GGS do not have a pathogenic variant identified in either gene. We report on a 17-year-old female referred to the Undiagnosed Disease Network with a clinical diagnosis of GGS that manifested as both classic and unusual findings, including isolated hypogonadotropic hypogonadism and anosmia (Kallmann syndrome), orofacial cleft, and abnormal semicircular canals (SCC). Prior genetic testing, including a targeted gene panel, genomic microarray, exome sequencing, and genome sequencing, was non-diagnostic, although these studies identified a variant of uncertain significance in CHD7, which may have contributed to elements of the phenotype (e.g., abnormal SCC). Reanalysis of genome sequencing data using research analytic methods, together with karyotyping, FISH, and Sanger sequencing, identified a novel de novo paracentric inversion that truncated PTCH1. These findings underscore the value of in-depth phenotype-guided genomic analysis, including chromosomal structural variants, as well as the occurrence of possible dual genetic diagnoses in the same individuals. Moreover, the definitive diagnosis provided the patient and family with a firmer basis for management and counseling.

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• Does estradiol supplementation improve rotator cuff repair outcomes in postmenopausal women?

  JSES Reviews Reports and Techniques · 2025-12-12

  articleOpen access

  <h2>Abstract</h2><h3>Background</h3> Although rotator cuff tears (RCT) are one the most common musculoskeletal sources of disability, healing after rotator cuff repair (RCR) fails in >25% of cases. Existing data suggests that estradiol deficiency may be associated with worse postoperative outcomes following RCR. Thus, the purpose of this study was to determine whether estradiol supplementation among postmenopausal women is associated with better outcomes after RCR and we hypothesized that such an association would exist. <h3>Methods</h3> A retrospective review of all patients who underwent RCR by the lead author was done to identify those who were female and ≥50-years-old, thus presumed to be postmenopausal. For all patients, all medications were recorded the day of surgery by the anesthesiologist in the pre-anesthesia note. These notes were reviewed to determine which patients were taking hormone replacement therapy (ie. "HRT") and those who were not (i.e. "non-HRT") at the time of surgery. All patients were contacted at two years postoperatively. Subjective shoulder value (SSV), visual analogue scale for pain (VAS), and American Shoulder and Elbow Surgeons (ASES) score were collected, in addition to satisfaction and need for further reoperation. <h3>Results</h3> Overall, 254 women underwent RCR, of whom two-year outcomes were obtained in 184 (74%) of which 42 (23%) were on estradiol supplementation at the time of surgery. There were no differences between groups in preoperative SSV (43±21 non-HRT vs. 38±22 HRT, p=0.209), VAS (5.6±2.3 vs. 5.7±2.3, p=0.770), or ASES scores (46±20 vs. 44±19, p=0.738). However, HRT postmenopausal patients had significantly better VAS (1.2±2.1 vs. 0.3±0.8, p<0.001) and SSV scores (87±16 vs. 95±10, p=0.003) at 2-years postoperatively when compared to non-HRT postmenopausal patients. There were no significant differences in satisfaction (96.3% vs. 90.3%, p=0.605), ASES scores (87±17 vs. 94±11, p=0.146), or reoperation rates (7.9% vs. 14.8%, p=0.297). <h3>Conclusion</h3> Estradiol supplementation was associated with better outcomes in postmenopausal women undergoing RCR, however these differences in VAS and SSV did not meet the minimal clinically important threshold. Future prospective randomized studies could be considered before prescribing estradiol to post-menopausal patients in the setting of RCR.

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• An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

  Genome Medicine · 2025-10-21 · 7 citations

  articleOpen access

  BACKGROUND: Exome sequencing (ES) and genome sequencing (GS) are increasingly used as standard genetic tests to identify diagnostic variants in rare disease cases. However, prioritizing these variants to reduce the time and burden of manual interpretation by clinical teams remains a significant challenge. The Exomiser/Genomiser software suite is the most widely adopted open-source software for prioritizing coding and noncoding variants. Despite its ubiquitous use, limited data-driven guidelines currently exist to optimize its performance for diagnostic variant prioritization. Based on detailed analyses of Undiagnosed Diseases Network (UDN) probands, this study presents optimized parameters and practical recommendations for deploying the Exomiser and Genomiser tools. We also highlight scenarios where diagnostic variants may be missed and propose alternative workflows to improve diagnostic success in such complex cases. METHODS: We analyzed 386 diagnosed probands from the UDN, including cases with coding and noncoding diagnostic variants. We systematically evaluated how tool performance was affected by key parameters, including gene:phenotype association data, variant pathogenicity predictors, phenotype term quality and quantity, and the inclusion and accuracy of family variant data. RESULTS: Parameter optimization significantly improved Exomiser's performance over default parameters. For GS data, the percentage of coding diagnostic variants ranked within the top 10 candidates increased from 49.7% to 85.5%, and for ES, from 67.3% to 88.2%. For noncoding variants prioritized with Genomiser, the top 10 rankings improved from 15.0% to 40.0%. We also explored refinement strategies for Exomiser outputs, including using p-value thresholds and flagging genes that are frequently ranked in the top 30 candidates but rarely associated with diagnoses. CONCLUSION: This study provides an evidence-based framework for variant prioritization in ES and GS data using Exomiser and Genomiser. These recommendations have been implemented in the Mosaic platform to support the ongoing analysis of undiagnosed UDN participants and provide efficient, scalable reanalysis to improve diagnostic yield. Our work also highlights the importance of tracking solved cases and diagnostic variants that can be used to benchmark bioinformatics tools. Exomiser and Genomiser are available at https://github.com/exomiser/Exomiser/ .

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01FD003014

  NIH · $658k · 2009

• The Genetics of Primary Ovarian Insufficiency

  NIH · $300k · 2017–2019

• NIH Grant R01HD065029

  NIH · $1.7M · 2015

• NIH Grant M01RR002635

  NIH · $27.3M · 2010

• NIH Grant M01RR001066

  NIH · $3.7M · 2008

Frequent coauthors

• Janet E. Hall

  National Institute of Environmental Health Sciences

  78 shared

• Kathryn A. Martin

  61 shared

• William F. Crowley

  Massachusetts General Hospital

  55 shared

• Lacey Plummer

  Massachusetts General Hospital

  50 shared

• Nelly Pitteloud

  University of Lausanne

  48 shared

• Stephanie B. Seminara

  Massachusetts General Hospital

  47 shared

• Judith Adams

  University of Otago

  45 shared

• Richard Quinton

  Imperial College London

  44 shared

Education

• M.D.

  Cornell

• M.D.

  Brigham and Women’s

• M.D.

  Mass General