Michael F Christman

Coriell Institute for Medical Research, Camden, New Jersey, United States

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Publications (89)502.37 Total impact

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    ABSTRACT: Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine.
    Full-text · Article · Jan 2016 · Expert Review of Molecular Diagnostics
  • Susan K Delaney · Michael F Christman
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    ABSTRACT: The direct-to-consumer genetic testing debate reached a fever pitch in November 2013 when the US Food and Drug Administration (FDA) instructed 23andMe to discontinue marketing and sale of their Personal Genome Service. In 2015, 23andMe emerged with FDA approval to market a carrier test for Bloom syndrome only, and plans to release additional reports. The dust has settled and it is time to ask: What have we learned, and where do we go from here?
    No preview · Article · Oct 2015 · Clinical Pharmacology &#38 Therapeutics
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    ABSTRACT: Genetic literacy is essential for the effective integration of genomic information into healthcare; yet few recent studies have been conducted to assess the current state of this knowledge base. Participants in the Coriell Personalized Medicine Collaborative (CPMC), a prospective study assessing the impact of personalized genetic risk reports for complex diseases and drug response on behavior and health outcomes, completed genetic knowledge questionnaires and other surveys through an online portal. To assess the association between genetic knowledge and genetic education background, multivariate linear regression was performed. 4 062 participants completed a genetic knowledge and genetic education background questionnaire. Most were older (mean age: 50), Caucasian (90 %), female (59 %), highly educated (69 % bachelor's or higher), with annual household income over $100 000 (49 %). Mean percent correct was 76 %. Controlling for demographics revealed that health care providers, participants previously exposed to genetics, and participants with 'better than most' self-rated knowledge were significantly more likely to have a higher knowledge score (p < 0.001). Overall, genetic knowledge was high with previous genetic education experience predictive of higher genetic knowledge score. Education is likely to improve genetic literacy, an important component to expanded use of genomics in personalized medicine.
    Full-text · Article · Aug 2015 · Journal of Genetic Counseling
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    ABSTRACT: There is currently great interest in using genetic risk estimates for common disease in personalized healthcare. Here we assess melanoma risk-related preventive behavioral change in the context of the Coriell Personalized Medicine Collaborative (CPMC). As part of on-going reporting activities within the project, participants received a personalized risk assessment including information related to their own self-reported family history of melanoma and a genetic risk variant showing a moderate effect size (1.7, 3.0 respectively for heterozygous and homozygous individuals). Participants who opted to view their report were sent an optional outcome survey assessing risk perception and behavioral change in the months that followed. Participants that report family history risk, genetic risk, or both risk factors for melanoma were significantly more likely to increase skin cancer preventive behaviors when compared to participants with neither risk factor (ORs = 2.04, 2.79, 4.06 and p-values = 0.02, 2.86 × 10-5, 4.67 × 10-5, respectively), and we found the relationship between risk information and behavior to be partially mediated by anxiety. Genomic risk assessments appear to encourage positive behavioral change in a manner that is complementary to family history risk information and therefore may represent a useful addition to standard of care for melanoma prevention.
    Full-text · Article · Mar 2015
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    ABSTRACT: Large-scale sequencing information may provide a basis for genetic tests for predisposition to common disorders. In this study, participants in the Coriell Personalized Medicine Collaborative (N = 53) with a personal and/or family history of Major Depressive Disorder or Bipolar Disorder were interviewed based on the Health Belief Model around hypothetical intention to test one’s children for probability of developing a mood disorder. Most participants (87 %) were interested in a hypothetical test for children that had high (“90 %”) positive predictive value, while 51 % of participants remained interested in a modestly predictive test (“20 %”). Interest was driven by beliefs about effects of test results on parenting behaviors and on discrimination. Most participants favored testing before adolescence (64 %), and were reluctant to share results with asymptomatic children before adulthood. Participants anticipated both positive and negative effects of testing on parental treatment and on children’s self-esteem. Further investigation will determine whether these findings will generalize to other complex disorders for which early intervention is possible but not clearly demonstrated to improve outcomes. More information is also needed about the effects of childhood genetic testing and sharing of results on parent–child relationships, and about the role of the child in the decision-making process. Electronic supplementary material The online version of this article (doi:10.1007/s10897-014-9710-y) contains supplementary material, which is available to authorized users.
    Preview · Article · Mar 2014 · Journal of Genetic Counseling
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    ABSTRACT: Use of genomic information in healthcare is increasing; however data on the needs of consumers of genomic information is limited. The Coriell Personalized Medicine Collaborative (CPMC) is a longitudinal study investigating the utility of personalized medicine. Participants receive results reflecting risk of common complex conditions and drug-gene pairs deemed actionable by an external review board. To explore the needs of individuals receiving genomic information we reviewed all genetic counseling sessions with CPMC participants. A retrospective qualitative review of notes from 157 genetic counseling inquiries was conducted. Notes were coded for salient themes. Five primary themes; "understanding risk", "basic genetics", "complex disease genetics", "what do I do now?" and "other" were identified. Further review revealed that participants had difficulty with basic genetic concepts, confused relative and absolute risks, and attributed too high a risk burden to individual single nucleotide polymorphisms (SNPs). Despite these hurdles, counseled participants recognized that behavior changes could potentially mitigate risk and there were few comments alluding to an overly deterministic or fatalistic interpretation of results. Participants appeared to recognize the multifactorial nature of the diseases for which results were provided; however education to understand the complexities of genomic risk information was often needed.
    No preview · Article · Feb 2014 · Journal of Genetic Counseling
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    ABSTRACT: We describe the development and implementation of a randomized controlled trial to investigate the impact of genomic counseling on a cohort of patients with heart failure (HF) or hypertension (HTN), managed at a large academic medical center, the Ohio State University Wexner Medical Center (OSUWMC). Our study is built upon the existing Coriell Personalized Medicine Collaborative (CPMC®). OSUWMC patient participants with chronic disease (CD) receive eight actionable complex disease and one pharmacogenomic test report through the CPMC® web portal. Participants are randomized to either the in-person post-test genomic counseling—active arm, versus web-based only return of results—control arm. Study-specific surveys measure: (1) change in risk perception; (2) knowledge retention; (3) perceived personal control; (4) health behavior change; and, for the active arm (5), overall satisfaction with genomic counseling. This ongoing partnership has spurred creation of both infrastructure and procedures necessary for the implementation of genomics and genomic counseling in clinical care and clinical research. This included creation of a comprehensive informed consent document and processes for prospective return of actionable results for multiple complex diseases and pharmacogenomics (PGx) through a web portal, and integration of genomic data files and clinical decision support into an EPIC-based electronic medical record. We present this partnership, the infrastructure, genomic counseling approach, and the challenges that arose in the design and conduct of this ongoing trial to inform subsequent collaborative efforts and best genomic counseling practices.
    Full-text · Article · Jan 2014
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    Full-text · Dataset · Nov 2013
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    Full-text · Dataset · Nov 2013
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    ABSTRACT: Obesity rates in the United States have escalated in recent decades and present a major challenge in public health prevention efforts. Currently, testing to identify genetic risk for obesity is readily available through several direct-to-consumer companies. Despite the availability of this type of testing, there is a paucity of evidence as to whether providing people with personal genetic information on obesity risk will facilitate or impede desired behavioral responses. We describe the key issues in the design and implementation of a randomized controlled trial examining the clinical utility of providing genetic risk information for obesity. Participants are being recruited from the Coriell Personalized Medicine Collaborative, an ongoing, longitudinal research cohort study designed to determine the utility of personal genome information in health management and clinical decision making. The primary focus of the ancillary Obesity Risk Communication Study is to determine whether genetic risk information added value to traditional communication efforts for obesity, which are based on lifestyle risk factors. The trial employs a 2 × 2 factorial design in order to examine the effects of providing genetic risk information for obesity, alone or in combination with lifestyle risk information, on participants' psychological responses, behavioral intentions, health behaviors, and weight. The factorial design generated four experimental arms based on communication of estimated risk to participants: (1) no risk feedback (control), (2) genetic risk only, (3) lifestyle risk only, and (4) both genetic and lifestyle risk (combined). Key issues in study design pertained to the selection of algorithms to estimate lifestyle risk and determination of information to be provided to participants assigned to each experimental arm to achieve a balance between clinical standards and methodological rigor. Following the launch of the trial in September 2011, implementation challenges pertaining to low enrollment and differential attrition became apparent and required immediate attention and modifications to the study protocol. Although monitoring of these efforts is ongoing, initial observations show a doubling of enrollment and reduced attrition. The trial is evaluating the short-term impact of providing obesity risk information as participants are followed for only 3 months. This study is built upon the structure of an existing personalized medicine study wherein participants have been provided with genetic information for other diseases. This nesting in a larger study may attenuate the effects of obesity risk information and has implications for the generalizability of study findings. This randomized trial examines value of obesity genetic information, both when provided independently and when combined with lifestyle risk assessment, to motivate individuals to engage in healthy lifestyle behaviors. Study findings will guide future intervention efforts to effectively communicate genetic risk information.
    Preview · Article · Nov 2013 · Clinical Trials
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    ABSTRACT: Implementation of pharmacogenomics (PGx) in clinical care can lead to improved drug efficacy and reduced adverse drug reactions. However, there has been a lag in adoption of PGx tests in clinical practice. This is due in part to a paucity of rigorous systems for translating published clinical and scientific data into standardized diagnostic tests with clear therapeutic recommendations. Here we describe the Pharmacogenomics Appraisal, Evidence Scoring and Interpretation System (PhAESIS), developed as part of the Coriell Personalized Medicine Collaborative research study, and its application to seven commonly prescribed drugs.
    Full-text · Article · Oct 2013 · Genome Medicine
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    ABSTRACT: The Human Genetic Cell Repository sponsored by the National Institute of General Medical Sciences contains more than 11,000 cell lines and DNA samples collected from numerous individuals. All of these cell lines and DNA samples are categorized into several collections representing a variety of disease states, chromosomal abnormalities, heritable diseases, distinct human populations and apparently healthy individuals. Many of these cell lines have previously been studied with detailed conventional cytogenetic analyses including G-banded karyotyping and fluorescence in situ hybridization. This work was carried out by investigators at submitting institutions and scientists at Coriell Institute for Medical Research, where the NIGMS Repository is hosted. Recently, approximately 900 cell lines, mostly chosen from the Chromosomal Aberrations and Heritable Diseases collections, have been further characterized in detail at the Coriell Institute using the Affymetrix Genome-Wide Human SNP Array 6.0 to detect copy number variations and copy number neutral loss of heterozygosity. A database containing detailed cytogenetic and genomic information for these cell lines has been constructed and is freely available through several sources, such as the NIGMS Repository website and the UCSC Genome Browser. As additional cell lines are analyzed and subsequently added into it, the database will be maintained dynamically.
    Full-text · Article · May 2013 · G3-Genes Genomes Genetics
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    ABSTRACT: Top SNPs for GWAS of HDL.
    Preview · Dataset · Sep 2012
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    ABSTRACT: Allele Frequency Comparison for Tested Loci that were not Transferable.
    Preview · Dataset · Sep 2012
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    ABSTRACT: Background A recent, large genome-wide association study (GWAS) of European ancestry individuals has identified multiple genetic variants influencing serum lipids. Studies of the transferability of these associations to African Americans remain few, an important limitation given interethnic differences in serum lipids and the disproportionate burden of lipid-associated metabolic diseases among African Americans. Methods We attempted to evaluate the transferability of 95 lipid-associated loci recently identified in European ancestry individuals to 887 non-diabetic, unrelated African Americans from a population-based sample in the Washington, DC area. Additionally, we took advantage of the generally reduced linkage disequilibrium among African ancestry populations in comparison to European ancestry populations to fine-map replicated GWAS signals. Results We successfully replicated reported associations for 10 loci (CILP2/SF4, STARD3, LPL, CYP7A1, DOCK7/ANGPTL3, APOE, SORT1, IRS1, CETP, and UBASH3B). Through trans-ethnic fine-mapping, we were able to reduce associated regions around 75% of the loci that replicated. Conclusions Between this study and previous work in African Americans, 40 of the 95 loci reported in a large GWAS of European ancestry individuals also influence lipid levels in African Americans. While there is now evidence that the lipid-influencing role of a number of genetic variants is observed in both European and African ancestry populations, the still considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of these traits.
    Full-text · Article · Sep 2012 · BMC Medical Genetics
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    Dataset: Figure S2
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    ABSTRACT: Principal components analysis. Red represents CEU, blue represents YRI, and black represents the HUFS sample. Only the first principal component explained a significant amount of genetic variance. (PNG)
    Preview · Dataset · Sep 2012
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    ABSTRACT: The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.
    Full-text · Article · Sep 2012 · PLoS ONE
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    Dataset: Figure S5
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    ABSTRACT: Density plots. The phenotypic distribution of eGFR was Box-Cox transformed to reduce skew using the transformation with the maximum likelihood estimate . The resulting distribution was winsorized at ±3 SD to reduce kurtosis. These adjustments reduced skew from 2.4 to −0.1 and reduced kurtosis from 25.2 to 1.0. Units for unadjusted glomerular filtration rate are mL/min/1.73 m2. (PDF)
    Preview · Dataset · Sep 2012
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    Dataset: Figure S4
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    ABSTRACT: Genome-wide distribution of admixture proportion. (PNG)
    Preview · Dataset · Sep 2012
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    Dataset: Table S3
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    ABSTRACT: Significant secondary associations. (DOC)
    Preview · Dataset · Sep 2012

Publication Stats

4k Citations
502.37 Total Impact Points

Institutions

  • 2009-2015
    • Coriell Institute for Medical Research
      Camden, New Jersey, United States
  • 2013
    • Emory University
      • Department of Human Genetics
      Atlanta, Georgia, United States
  • 2001-2008
    • Boston University
      • Genetics and Genomics
      Boston, Massachusetts, United States
  • 2003
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1999-2001
    • University of Virginia
      • Microbiology, Immunology and Cancer Biology (MIC)
      Charlottesville, Virginia, United States
  • 1993-1996
    • University of California, San Francisco
      • Department of Radiation Oncology
      San Francisco, California, United States