Bio


Dr. Vikram Fielding-Singh is a Clinical Assistant Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University. He obtained his medical degree from Stanford University and completed residency training at the University of California, San Francisco. He then pursued dual cardiac anesthesia and critical care training at the University of California, Los Angeles. He holds a juris doctorate from Yale Law School. Dr. Fielding-Singh’s research interests include improving perioperative care of patients with end stage kidney disease, using biomarkers to aid early diagnosis of acute kidney injury, and evaluating the performance of risk prediction models in perioperative medicine.

Clinical Focus


  • Anesthesia
  • Cardiothoracic Anesthesiology
  • Critical Care Medicine

Academic Appointments


Professional Education


  • Board Certification: National Board of Echocardiography, Advanced Perioperative Transesophageal Echocardiography (2020)
  • Board Certification: American Board of Anesthesiology, Critical Care Medicine (2020)
  • Board Certification: American Board of Anesthesiology, Anesthesia (2019)
  • Fellowship: UCLA Critical Care Fellowship Program (2020) CA
  • Fellowship: UCLA Adult Cardiothoracic Anesthesia Fellowship (2019) CA
  • Residency: UCSF Anesthesiology Residency (2018) CA
  • Internship: Kaiser Permanente San Francisco Internal Medicine Residency (2015) CA
  • Medical Education: Stanford University School of Medicine (2014) CA
  • JD, Yale Law School (2010)

Current Research and Scholarly Interests


I am a clinical investigator interested in improving perioperative care of patients with end stage kidney disease, using biomarkers to aid early diagnosis of acute kidney injury, optimizing care for high-risk cardiac surgical patients and those on mechanical circulatory support, and evaluating the performance of risk prediction models in perioperative medicine.

Clinical Trials


  • Strategies for Anticoagulation During Venovenous ECMO Recruiting

    Moderate intensity titrated dose anticoagulation has been used in patients receiving extracorporeal membrane oxygenation (ECMO) to prevent thromboembolism and thrombotic mechanical complications. As technology has improved, however, the incidence of thromboembolic events has decreased, leading to re-evaluation of the risks of anticoagulation, particularly during venovenous (V-V) ECMO. Recent data suggest that bleeding complications during V-V ECMO may be more strongly associated with mortality than thromboembolic complications, and case series have suggested that V-V ECMO can be safely performed without moderate or high intensity anticoagulation. At present, there is significant variability between institutions in the approach to anticoagulation during V-V ECMO. A definitive randomized controlled trial is needed to compare the effects of a low intensity fixed dose anticoagulation (low intensity) versus moderate intensity titrated dose anticoagulation (moderate intensity) on clinical outcomes during V-V ECMO. Before such a trial can be conducted, however, additional data are needed to inform the feasibility of the future trial.

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All Publications


  • The Society of Thoracic Surgeons Adult Cardiac Surgery Database: Intraoperative Echocardiography Reporting. Journal of cardiothoracic and vascular anesthesia Nicoara, A., Fielding-Singh, V., Bollen, B. A., Rhee, A., Mackay, E. J., Abernathy, J. H., Alfirevic, A., John, S., Kapoor, A., MacDonald, A. J., Qu, J. Z., Roca, G. Q., Subramanian, H., Kertai, M. D. 2024

    Abstract

    To identify trends in the reporting of intraoperative transesophageal echocardiographic (TEE) data in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) and the Adult Cardiac Anesthesiology (ACA) module by period, practice type, and geographic distribution, and to elucidate ongoing areas for practice improvement.A retrospective study.STS ACSD.Procedures reported in the STS ACSD between July 2017 and December 2021 in participating programs in the United States.None MEASUREMENTS AND MAIN RESULTS: Intraoperative TEE is reported for 73% of all procedures in ACSD. Although the intraoperative TEE data reporting rate increased from 2017 to 2021 for isolated coronary artery bypass graft surgery, it remained low at 62.2%. The reporting of relevant echocardiographic variables across a wide range of procedures has steadily increased over the study period but also remained low. The reporting in the ACA module is high for most variables and across all anesthesia care models; however, the overall contribution of the ACA module to the ACSD remains low.This progress report suggests a continued need to raise awareness regarding current practices of reporting intraoperative TEE in the ACSD and the ACA, and highlights opportunities for improving reporting and data abstraction.

    View details for DOI 10.1053/j.jvca.2024.01.009

    View details for PubMedID 38365466

  • Variability and relative contribution of surgeon and anesthesia specific time components to total procedural time in cardiac surgery. The Journal of thoracic and cardiovascular surgery Vanneman, M. W., Thuraiappah, M., Feinstein, I., Fielding-Singh, V., Peterson, A., Kronenberg, S., Angst, M. S., Aghaeepour, N. 2023

    Abstract

    OBJECTIVES: Decreasing variability in time intensive tasks during cardiac surgery may reduce total procedural time, lower costs, reduce clinician burnout, and improve patient access. The relative contribution and variability of surgeon and anesthesia control times to total procedural time is unknown.METHODS: 669 patients undergoing coronary artery bypass graft surgery were enrolled. Using linear regression, we estimated adjusted surgeon and anesthesia control times controlling for patient and procedural covariates. The primary end point compared overall surgeon and anesthesia control times. The secondary end point compared the variability in adjusted surgeon and anesthesiologist control times. Sensitivity analyses quantified the relative importance of the specific surgeon and anesthesiologist in the adjusted linear models.RESULTS: The median surgeon control time was 4.1 hours (interquartile range: 3.4 to 4.9 hours) compared to a median anesthesia control time of 1.0 hours (interquartile range: 0.8 to 1.2 hours, p < 0.001). Using linear regression, the variability in adjusted surgeon control time amongst surgeons (range: 1.8 hours) was 3.5-fold greater than the variability in adjusted anesthesia control time amongst anesthesiologists (range: 0.5 hours, p < 0.001). The specific surgeon and anesthesiologist accounted for 50% of the explanatory power of the predictive model (p < 0.001).CONCLUSIONS: Surgeon control time variability is significantly greater than anesthesia control time variability and strongly associated with the surgeon performing the procedure. While these results suggest surgeon control time variability is an attractive operational target, further studies are needed to determine practitioner specific and modifiable attributes to reduce variability and improve efficiency.

    View details for DOI 10.1016/j.jtcvs.2023.08.011

    View details for PubMedID 37574007

  • Disparities in the Timing of Preoperative Hemodialysis Among Patients With End-Stage Kidney Disease. JAMA network open Fielding-Singh, V., Vanneman, M. W., Morris, A. M., Chertow, G. M., Lin, E. 2023; 6 (7): e2326326

    View details for DOI 10.1001/jamanetworkopen.2023.26326

    View details for PubMedID 37505500

  • Clinically Indicated, Equitable Care for Ischemic Heart Disease in CKD: A Call to Action. Journal of the American Society of Nephrology : JASN Fielding-Singh, V., Chertow, G. M. 2023; 34 (4): 525-526

    View details for DOI 10.1681/ASN.0000000000000100

    View details for PubMedID 37000953

  • Preoperative Hemodialysis Timing and Postoperative Mortality in Patients With End-stage Kidney Disease-Reply. JAMA Fielding-Singh, V., Vanneman, M. W., Lin, E. 2023; 329 (11): 939-940

    View details for DOI 10.1001/jama.2022.24891

    View details for PubMedID 36943217

  • The Art of the Null Hypothesis-Considerations for Study Design and Scientific Reporting. Journal of cardiothoracic and vascular anesthesia O'Donnell, C. T., Fielding-Singh, V., Vanneman, M. W. 2023

    View details for DOI 10.1053/j.jvca.2023.02.026

    View details for PubMedID 36933992

  • Variations in operating room staff compliance with mandatory daily electronic COVID-19 symptom screening. British journal of anaesthesia Gessner, D. M., Sun, E., Fielding-Singh, V. 2023; 130 (1): e10-e12

    View details for DOI 10.1016/j.bja.2022.09.014

    View details for PubMedID 36939494

  • Association Between Preoperative Hemodialysis Timing and Postoperative Mortality in Patients With End-stage Kidney Disease. JAMA Fielding-Singh, V., Vanneman, M. W., Grogan, T., Neelankavil, J. P., Winkelmayer, W. C., Chang, T. I., Liu, V. X., Lin, E. 2022

    Abstract

    For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown.To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis.Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018.One-, two-, or three-day intervals between the most recent hemodialysis treatment and the surgical procedure. Hemodialysis on the day of the surgical procedure vs no hemodialysis on the day of the surgical procedure.The primary outcome was 90-day postoperative mortality. The relationship between the dialysis-to-procedure interval and the primary outcome was modeled using a Cox proportional hazards model.Of the 1 147 846 surgical procedures among 346 828 patients (median age, 65 years [IQR, 56-73 years]; 495 126 procedures [43.1%] in female patients), 750 163 (65.4%) were performed when the last hemodialysis session occurred 1 day prior to surgery, 285 939 (24.9%) when the last hemodialysis session occurred 2 days prior to surgery, and 111 744 (9.7%) when the last hemodialysis session occurred 3 days prior to surgery. Hemodialysis was also performed on the day of surgery for 193 277 procedures (16.8%). Ninety-day postoperative mortality occurred after 34 944 procedures (3.0%). Longer intervals between the last hemodialysis session and surgery were significantly associated with higher risk of 90-day mortality in a dose-dependent manner (2 days vs 1 day: absolute risk, 4.7% vs 4.2%, absolute risk difference, 0.6% [95% CI, 0.4% to 0.8%], adjusted hazard ratio [HR], 1.14 [95% CI, 1.10 to 1.18]; 3 days vs 1 day: absolute risk, 5.2% vs 4.2%, absolute risk difference, 1.0% [95% CI, 0.8% to 1.2%], adjusted HR, 1.25 [95% CI, 1.19 to 1.31]; and 3 days vs 2 days: absolute risk, 5.2% vs 4.7%, absolute risk difference, 0.4% [95% CI, 0.2% to 0.6%], adjusted HR, 1.09 [95% CI, 1.04 to 1.13]). Undergoing hemodialysis on the same day as surgery was associated with a significantly lower hazard of mortality vs no same-day hemodialysis (absolute risk, 4.0% for same-day hemodialysis vs 4.5% for no same-day hemodialysis; absolute risk difference, -0.5% [95% CI, -0.7% to -0.3%]; adjusted HR, 0.88 [95% CI, 0.84-0.91]). In the analyses that evaluated the interaction between the hemodialysis-to-procedure interval and same-day hemodialysis, undergoing hemodialysis on the day of the procedure significantly attenuated the risk associated with a longer hemodialysis-to-procedure interval (P<.001 for interaction).Among Medicare beneficiaries with end-stage kidney disease, longer intervals between hemodialysis and surgery were significantly associated with higher risk of postoperative mortality, mainly among those who did not receive hemodialysis on the day of surgery. However, the magnitude of the absolute risk differences was small, and the findings are susceptible to residual confounding.

    View details for DOI 10.1001/jama.2022.19626

    View details for PubMedID 36326747

  • Transcatheter Aortic Valve Dissemination: The More the Merrier or Too Much of a Good Thing? Journal of cardiothoracic and vascular anesthesia Bodmer, N. J., Fielding-Singh, V., Vanneman, M. W. 1800

    View details for DOI 10.1053/j.jvca.2021.11.023

    View details for PubMedID 34974961

  • Accuracy of administrative database estimates of national surgical Volume: Solid organ transplantation in the national inpatient sample. Clinical transplantation Fielding-Singh, V., Grogan, T. R., Neelankavil, J. P. 2021

    Abstract

    Little is known about the accuracy of procedural coding in the National Inpatient Sample, in part because it is challenging to validate population-level estimates. We evaluated the accuracy of the National Inpatient Sample by comparing estimates of solid organ transplantation to known national transplant volumes from the Organ Procurement and Transplant Network. The mean deviation of National Inpatient Sample point estimates from true transplant volume for the study period was 17.5 ± 20.8%. The mean deviation of point estimates from 2005-2011 was 26.4 ± 22.8% compared to 4.9 ± 6.3% from 2012-2016 (p < .001). Although future National Inpatient Sample transplantation research may be limited by the inability to subgroup procedures by donor type, surgical procedure coding of solid organ transplantation within the National Inpatient Sample appears to be accurate and reliable for generating national estimates, particularly after the National Inpatient Sample redesign in 2012. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/ctr.14441

    View details for PubMedID 34297431

  • Predicting Post-Liver Transplant Outcomes-Rise of the Machines or a Foggy Crystal Ball? Journal of cardiothoracic and vascular anesthesia Vanneman, M. W., Fielding-Singh, V., Aghaeepour, N. 2021

    View details for DOI 10.1053/j.jvca.2021.03.012

    View details for PubMedID 33846080

  • Impact of the Addition of Examples to the American Society of Anesthesiologists Physical Status Classification System ANESTHESIA AND ANALGESIA Fielding-Singh, V., Willingham, M. D., Grogan, T., Neelankavil, J. P. 2020; 130 (3): E54–E57

    Abstract

    Examples of comorbidities for the widely used American Society of Anesthesiologists physical status (ASA-PS) classification system were developed and approved in 2014. We conducted a retrospective cohort study of patients with 4 comorbidities included in the examples as warranting a specific minimum ASA-PS class. For each comorbidity subgroup, we used interrupted time-series models to compare ASA-PS underclassification for the periods before (2011-2014) and after (2015-2017) the introduction of examples. Rates of underclassification ranged from 4.8% to 38.7%. We observed no evidence of a significant impact on ASA-PS classification with the introduction of examples in 2014.

    View details for DOI 10.1213/ANE.0000000000004482

    View details for Web of Science ID 000528834100003

    View details for PubMedID 31651457

  • A Population-Based Analysis of Intraoperative Cardiac Arrest in the United States ANESTHESIA AND ANALGESIA Fielding-Singh, V., Willingham, M. D., Fischer, M. A., Grogan, T., Benharash, P., Neelankavil, J. P. 2020; 130 (3): 627–34

    Abstract

    A new billable code for intraoperative cardiac arrest was introduced with the International Classification of Diseases, Tenth Revision, classification system. Using a national administrative database, we performed a retrospective analysis of intraoperative cardiac arrest in the United States.Hospital admissions involving patients ≥18 years of age who underwent operating room procedures in 2016 were identified using the National Inpatient Sample. The primary outcome was the incidence of intraoperative cardiac arrest. Secondary outcomes included total cost of admission, in-hospital mortality, length of stay, and identification of risk factors associated with intraoperative cardiac arrest. Clinical risk factors were evaluated with multivariable logistic regression models using sampling weights and adjustment for clustering by strata.Of 35,675,421 admissions in 2016 in the United States, 9,244,861 admissions were identified in patients ≥18 years of age who underwent at least one operating room procedure. An estimated 5230 hospital admissions involved intraoperative cardiac arrest, yielding an estimated incidence of 5.7 (95% confidence interval [CI], 5.3-6.0) per 10,000 hospital admissions. Admissions involving an intraoperative cardiac arrest had a 35.7% in-hospital mortality, compared with 1.3% for admissions without intraoperative cardiac arrest. Intraoperative cardiac arrest was associated with a 15.44-fold (95% CI, 12.74-18.70; P < .001) increase in the risk-adjusted odds of in-hospital mortality and an additional $13,184 (95% CI, 9600-16,769; P < .001) of total admission costs. Selected factors independently associated with increased risk-adjusted odds of intraoperative cardiac arrest included: black or missing race; cardiac, thoracic, or vascular surgery; congestive heart failure; pulmonary circulation disorders; peripheral vascular disease; end-stage renal disease; and fluid and electrolyte disorders.In this population-based study of intraoperative cardiac arrest in the United States, admissions involving an intraoperative cardiac arrest were rare but were associated with high in-hospital mortality.

    View details for DOI 10.1213/ANE.0000000000004477

    View details for Web of Science ID 000528834100037

    View details for PubMedID 31651456

  • Methylprednisolone: Likely an Effective Treatment in Acute Respiratory Distress Syndrome Reply CRITICAL CARE MEDICINE Fielding-Singh, V., Matthay, M. A., Calfee, C. S. 2019; 47 (4): E375–E376

    View details for DOI 10.1097/CCM.0000000000003648

    View details for Web of Science ID 000469386100014

    View details for PubMedID 30882440

    View details for PubMedCentralID PMC6467538

  • Airway Pressure Release Ventilation as a Rescue for Acute Respiratory Distress Syndrome But Use Early to Prevent It! Reply CRITICAL CARE MEDICINE Fielding-Singh, V., Matthay, M. A., Calfee, C. S. 2019; 47 (4): E380–E381

    View details for DOI 10.1097/CCM.0000000000003666

    View details for Web of Science ID 000469386100020

    View details for PubMedID 30882446

    View details for PubMedCentralID PMC6494106

  • Beyond Low Tidal Volume Ventilation: Treatment Adjuncts for Severe Respiratory Failure in Acute Respiratory Distress Syndrome CRITICAL CARE MEDICINE Fielding-Singh, V., Matthay, M. A., Calfee, C. S. 2018; 46 (11): 1820–31

    Abstract

    Despite decades of research, the acute respiratory distress syndrome remains associated with significant morbidity and mortality. This Concise Definitive Review provides a practical and evidence-based summary of treatments in addition to low tidal volume ventilation and their role in the management of severe respiratory failure in acute respiratory distress syndrome.We searched the PubMed database for clinical trials, observational studies, and review articles describing treatment adjuncts in acute respiratory distress syndrome patients, including high positive end-expiratory pressure strategies, recruitment maneuvers, high-frequency oscillatory ventilation, neuromuscular blockade, prone positioning, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, glucocorticoids, and renal replacement therapy.Results were reviewed by the primary author in depth. Disputed findings and conclusions were then reviewed with the other authors until consensus was achieved.Severe respiratory failure in acute respiratory distress syndrome may present with refractory hypoxemia, severe respiratory acidosis, or elevated plateau airway pressures despite lung-protective ventilation according to acute respiratory distress syndrome Network protocol. For severe hypoxemia, first-line treatment adjuncts include high positive end-expiratory pressure strategies, recruitment maneuvers, neuromuscular blockade, and prone positioning. For refractory acidosis, we recommend initial modest liberalization of tidal volumes, followed by neuromuscular blockade and prone positioning. For elevated plateau airway pressures, we suggest first decreasing tidal volumes, followed by neuromuscular blockade, modification of positive end-expiratory pressure, and prone positioning. Therapies such as inhaled pulmonary vasodilators, glucocorticoids, and renal replacement therapy have significantly less evidence in favor of their use and should be considered second line. Extracorporeal membrane oxygenation may be life-saving in selected patients with severe acute respiratory distress syndrome but should be used only when other alternatives have been applied.Severe respiratory failure in acute respiratory distress syndrome often necessitates the use of treatment adjuncts. Evidence-based application of these therapies in acute respiratory distress syndrome remains a significant challenge. However, a rational stepwise approach with frequent monitoring for improvement or harm can be achieved.

    View details for DOI 10.1097/CCM.0000000000003406

    View details for Web of Science ID 000447016100028

    View details for PubMedID 30247273

    View details for PubMedCentralID PMC6277052

  • Reply to the Timing of Early Antibiotics and Hospital Mortality in Sepsis - Playing Devil's Advocate. American journal of respiratory and critical care medicine Liu, V., Fielding-Singh, V., Iwashyna, T. J., Bhattacharya, J., Escobar, G. 2017

    View details for DOI 10.1164/rccm.201704-0774LE

    View details for PubMedID 28485627

  • The Timing of Early Antibiotics and Hospital Mortality in Sepsis. American journal of respiratory and critical care medicine Liu, V. X., Fielding-Singh, V., Greene, J. D., Baker, J. M., Iwashyna, T. J., Bhattacharya, J., Escobar, G. J. 2017

    Abstract

    Prior sepsis studies evaluating antibiotic timing have shown mixed results.To evaluate the association between antibiotic timing and mortality among sepsis patients receiving antibiotics within 6 hours of emergency department registration.Retrospective study of 35,000 randomly selected sepsis inpatients treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within six hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors.The median time to antibiotic administration was 2.1 hours (interquartile range: 1.4-3.1 hours). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% CI, 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hours delay in antibiotic administration was: 0.3% (95% CI, 0.01%-0.6%; p=0.04) for sepsis; 0.4% (95% CI, 0.1%-0.8%; p=0.02) for severe sepsis; and 1.8% (95% CI, 0.8%-3.0%; p=0.001) for shock.In a large, contemporary, and multicenter sample of sepsis patients in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients all of whom received antibiotics within 6 hours. The odds increased within each sepsis severity strata and the increased odds of mortality were greatest in septic shock.

    View details for DOI 10.1164/rccm.201609-1848OC

    View details for PubMedID 28345952

  • Ruling out bacteremia and bacterial meningitis in infants less than one month of age: is 48 hours of hospitalization necessary? Hospital pediatrics Fielding-Singh, V., Hong, D. K., Harris, S. J., Hamilton, J. R., Schroeder, A. R. 2013; 3 (4): 355-361

    Abstract

    The appropriate duration of hospitalization for infants ≤ 30 days admitted for fever or other concerns for a serious bacterial infection is an understudied area. We sought to determine the risk of a positive, pathogenic bacterial culture of blood or cerebrospinal fluid (CSF) in this population beyond 24 hours after collection.This study was a retrospective review of 1145 infants aged ≤30 days who had a blood or CSF culture from 1999 to 2010 at Santa Clara Valley Medical Center, a county health system in San Jose, California. Time to notification and the probability of a positive culture result after 24 hours were calculated. Infants were considered high risk if they had either a white blood cell count <5000 or >15 000 per µL, a band count >1500 per µL, or an abnormal urinalysis.We identified 1876 cultures (1244 blood, 632 CSF) in 1145 infants aged ≤30 days; 901 (79%) of 1145 were hospitalized and 408 (45%) of 901 hospitalizations were for fever without source (FWS). Thirty-one (2.7%) of the 1145 infants had pathogenic cultures; 6 of 1145 infants (0.5% [95% confidence interval: 0.2-1.1]) had a time to notification >24 hours. All 6 patients had FWS (1.5% of hospitalized FWS sample) and met high-risk criteria on presentation. No low-risk patients had a time to notification >24 hours. Low-risk characteristics were found in 57% (232 of 408) of the entire hospitalized FWS population.Low-risk infants hospitalized for FWS or other concerns for serious bacterial infection may not need hospitalization for a full 48 hours simply to rule out bacteremia and bacterial meningitis.

    View details for DOI 10.1542/hpeds.2013-0009

    View details for PubMedID 24435193

  • Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism NEURON Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., Chu, S. H., Moreau, M. P., Gupta, A. R., Thomson, S. A., Mason, C. E., Bilguvar, K., Celestino-Soper, P. B., Choi, M., Crawford, E. L., Davis, L., Wright, N. R., Dhodapkar, R. M., DiCola, M., DiLullo, N. M., Fernandez, T. V., Fielding-Singh, V., Fishman, D. O., Frahm, S., Garagaloyan, R., Goh, G. S., Kammela, S., Klei, L., Lowe, J. K., Lund, S. C., McGrew, A. D., Meyer, K. A., Moffat, W. J., Murdoch, J. D., O'Roak, B. J., Ober, G. T., Pottenger, R. S., Raubeson, M. J., Song, Y., Wang, Q., Yaspan, B. L., Yu, T. W., Yurkiewicz, L. R., Beaudet, A. L., Cantor, R. M., Curland, M., Grice, D. E., Guenel, M., Lifton, R. P., Mane, S. M., Martin, D. M., Shaw, C. A., Sheldon, M., Tischfield, J. A., Walsh, C. A., Morrow, E. M., Ledbetter, D. H., Fombonne, E., Lord, C., Martin, C. L., Brooks, A. I., Sutcliffe, J. S., Cook, E. H., Geschwind, D., Roeder, K., Devlin, B., State, M. W. 2011; 70 (5): 863-885

    Abstract

    We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.

    View details for DOI 10.1016/j.neuron.2011.05.002

    View details for Web of Science ID 000291843500008

    View details for PubMedID 21658581