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3. Whole Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized with Early-Onset Myocardial Infarction

Author

Khera, Amit V, Chaffin, Mark, Zekavat, Seyedeh M, Collins, Ryan L, Roselli, Carolina, Natarajan, Pradeep, Lichtman, Judith H, D'Onofrio, Gail, Mattera, Jennifer, Dreyer, Rachel, Spertus, John A, Taylor, Kent D, Psaty, Bruce M, Rich, Stephen S, Post, Wendy, Gupta, Namrata, Gabriel, Stacey, Lander, Eric, Ida Chen, Yii-Der, Talkowski, Michael E, Rotter, Jerome I, Krumholz, Harlan M, and Kathiresan, Sekar

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Health Sciences, Clinical Sciences, Sports Science and Exercise, Genetics, Clinical Research, Atherosclerosis, Human Genome, Prevention, Digestive Diseases, Heart Disease, Heart Disease - Coronary Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Aged, Cholesterol, LDL, Female, Genetic Predisposition to Disease, Genome, Human, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Multifactorial Inheritance, Myocardial Infarction, Whole Genome Sequencing, genetics, humans, hypercholesterolemia, myocardial infarction, risk, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundThe relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual.MethodsWe performed deep-coverage whole-genome sequencing of 2081 patients from 4 racial subgroups hospitalized in the United States with early-onset myocardial infarction (age ≤55 years) recruited with a 2:1 female-to-male enrollment design. We compared these genomes with those of 3761 population-based control subjects. We first identified individuals with a rare, monogenic mutation related to familial hypercholesterolemia. Second, we calculated a recently developed polygenic score of 6.6 million common DNA variants to quantify the cumulative susceptibility conferred by common variants. We defined high polygenic score as the top 5% of the control distribution because this cutoff has previously been shown to confer similar risk to that of familial hypercholesterolemia mutations.ResultsThe mean age of the 2081 patients presenting with early-onset myocardial infarction was 48 years, and 66% were female. A familial hypercholesterolemia mutation was present in 36 of these patients (1.7%) and was associated with a 3.8-fold (95% CI, 2.1-6.8; P3-fold increased odds of early-onset myocardial infarction. However, high polygenic score has a 10-fold higher prevalence among patients presents with early-onset myocardial infarction.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00597922.

Published
2019

4. Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease

Author

Emdin, Connor A, Khera, Amit V, Chaffin, Mark, Klarin, Derek, Natarajan, Pradeep, Aragam, Krishna, Haas, Mary, Bick, Alexander, Zekavat, Seyedeh M, Nomura, Akihiro, Ardissino, Diego, Wilson, James G, Schunkert, Heribert, McPherson, Ruth, Watkins, Hugh, Elosua, Roberto, Bown, Matthew J, Samani, Nilesh J, Baber, Usman, Erdmann, Jeanette, Gupta, Namrata, Danesh, John, Chasman, Daniel, Ridker, Paul, Denny, Joshua, Bastarache, Lisa, Lichtman, Judith H, D’Onofrio, Gail, Mattera, Jennifer, Spertus, John A, Sheu, Wayne H-H, Taylor, Kent D, Psaty, Bruce M, Rich, Stephen S, Post, Wendy, Rotter, Jerome I, Chen, Yii-Der Ida, Krumholz, Harlan, Saleheen, Danish, Gabriel, Stacey, and Kathiresan, Sekar

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Heart Disease - Coronary Heart Disease, Heart Disease, Biotechnology, Obesity, Cardiovascular, Human Genome, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Databases, Genetic, Diabetes Mellitus, Type 2, Disease, Gene Frequency, Genetic Testing, Genetic Variation, Humans, Phenotype, Proteins, Respiratory Hypersensitivity, United Kingdom
Abstract

Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency

Published
2018

7. Temperament

Author

Gartstein, Maria A., primary, Mattera, Jennifer, additional, and Hong Campagna, Allegra Xiu, additional

Published
2020
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13. Abstract 16514: Interpretation of Whole Genome Sequences for Risk of Early-Onset Myocardial Infarction

Author

Khera, Amit V, Zekavat, Seyedeh M, Chaffin, Mark, Roselli, Carolina, Natarajan, Pradeep, Klarin, Derek, Lichtman, Judith, DʼOnofrio, Gail, Mattera, Jennifer, Spertus, John, Sheu, Wayne, Taylor, Kent, Lin, Shih-Yi, Wang, Jun-Sing, Wang, Tzung-Dau, Juang, Jyh-Ming J, Dopazo, Ana, Bueno, Hector, Psaty, Bruce, Rich, Stephen S, Post, Wendy, Gupta, Namrata, Lander, Eric, Gabriel, Stacey, Rotter, Jerome, Chen, Yii-Der I, Krumholz, Harlan, and Kathiresan, Sekar

Published
2017

14. Using machine learning to understand age and gender classification based on infant temperament

Author

Gartstein, Maria A., primary, Seamon, D. Erich, additional, Mattera, Jennifer A., additional, Bosquet Enlow, Michelle, additional, Wright, Rosalind J., additional, Perez-Edgar, Koraly, additional, Buss, Kristin A., additional, LoBue, Vanessa, additional, Bell, Martha Ann, additional, Goodman, Sherryl H., additional, Spieker, Susan, additional, Bridgett, David J., additional, Salisbury, Amy L., additional, Gunnar, Megan R., additional, Mliner, Shanna B., additional, Muzik, Maria, additional, Stifter, Cynthia A., additional, Planalp, Elizabeth M., additional, Mehr, Samuel A., additional, Spelke, Elizabeth S., additional, Lukowski, Angela F., additional, Groh, Ashley M., additional, Lickenbrock, Diane M., additional, Santelli, Rebecca, additional, Du Rocher Schudlich, Tina, additional, Anzman-Frasca, Stephanie, additional, Thrasher, Catherine, additional, Diaz, Anjolii, additional, Dayton, Carolyn, additional, Moding, Kameron J., additional, and Jordan, Evan M., additional

Published
2022
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17. Telemonitoring in patients with heart failure

Author

Chaudhry, Sarwat I., Mattera, Jennifer A., Curtis, Jeptha P., Spertus, John A., Herrin, Jeph, Zhenqiu Lin, Philips, Christopher O., Hodshon, Beth V., Cooper, Lawton S., and Krumholz, Harlan M.

Subjects
Heart failure -- Patient outcomes, Telemedicine -- Patient outcomes, Hospital patients -- Care and treatment
Abstract

A randomized large scale trial was conducted among 1653 patients with recent history of hospitalization for heart failure to undergo either telemonitoring or usual care to determine possible effect of telemonitoring for improvement of heart-failure outcomes. Telemonitoring which failed to show any outcome improvements among patients recently hospitalized for heart failure indicated the significance of a thorough, independent evaluation of disease-management strategies before their adoption.

Published
2010

19. Prenatal internalizing symptoms as a potential mediator linking maternal adverse childhood experiences with infant temperament

Author

Mattera, Jennifer A.

Subjects
Infants--Development, Psychic trauma, Pregnancy--Psychological aspects, Pregnancy--Complications
Abstract

Adverse childhood experiences (ACEs), such as maltreatment and poverty, are commonly reported by women during the perinatal period. Although maternal ACEs have been found to significantly influence offspring development, the mechanisms currently linking maternal ACEs to socioemotional functioning during infancy remain largely unknown. The current study aimed to address this gap in the literature by examining whether internalizing symptoms during pregnancy mediate the association between maternal ACEs and infant temperament at two months. Moreover, this study investigated whether parenting practices during the postpartum period may buffer against the negative effects associated with maternal ACEs and prenatal internalizing symptoms on infant temperament. Secondary analyses were performed with existing data from a study investigating how factors such as nutrition, physical health, and psychosocial stress during pregnancy influence the development of infant temperament and stress reactivity (N=64). Participants completed several questionnaires during their third trimester of pregnancy, including measures assessing their early-life adversity as well as current depression and anxiety symptoms. At two months postpartum, mothers were administered an assessment measuring their infant's temperament and also participated in a parent-child interaction task designed to assess maternal sensitivity/responsiveness. Maternal ACEs was found to indirectly relate to the infant's ability to recover from stress via internalizing symptoms during pregnancy. Maternal sensitivity was also shown to moderate the effects of maternal ACEs and prenatal internalizing symptoms on infant temperament at two months. These results have implications for mental health screening procedures during pregnancy as well as the development of early intervention programs for infants born to mothers with early-life adversity.

Published
2020
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22. Strategies for reducing the door-to-balloon time in acute myocardial infarction

Author

Bradley, Elizabeth H., Herrin, Jeph, Wang, Yongfei, Barton, Barbara A., Webster, Tashonna R., Mattera, Jennifer A., Roumanis, Sarah A., Curtis, Jeptha P., Nallamothu, Brahmajee K., Magid, David J., McNamara, Robert L., Parkosewich, Janet, Loeb, Jerod M., and Krumholz, Harlan M.

Subjects
Heart attack -- Diagnosis, Heart attack -- Care and treatment, Cardiac catheterization -- Evaluation
Abstract

A study is conducted to examine different hospital strategies associated with a faster door-to-balloon time during primary percutaneous coronary intervention. Results show that many specific hospital strategies are associated with a significant reduction in the door-to-balloon time during treatment.

Published
2006

26. Clinical application of radionuclide angiography

Author

Port, Steven C., Wackers, Frans J. Th., Iskandrian, Abdulmassih S., Leppo, Jeffery A., Cerquiera, Manuel D., Verani, Mario S., Brown, Kenneth A., Bateman, Timothy M., Beller, George A., Berman, Daniel S., Bonow, Robert O., Garcia, Ernest V., Gibbons, Raymond J., Johnson, Lynne L., Mattera, Jennifer A., Schelbert, Heinrich R., Carretta, Robert, and Taillefer, Raymond

Published
1995
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30. The roles of senior management in quality improvement efforts: what are the key components?

Author

Bradley, Elizabeth H., Holmboe, Eric S., Mattera, Jennifer A., Roumanis, Sarah A., Radford, Martha J., and Krumholz, Harlan M.

Subjects
Quality control, Health care industry, Company business management, Quality control -- Methods, Management -- Methods, Medical errors -- Prevention, Health care industry -- Management, Hospitals -- Research
Abstract

EXECUTIVE SUMMARY With increasing attention directed at quality problems and medical errors in healthcare organizations, the ability of senior management to promote and sustain effective quality improvement efforts is paramount [...]

Published
2003

38. A Qualitative Study of Increasing [beta]-Blocker Use After Myocardial Infarction: Why Do Some Hospitals Succeed?

Author

Bradley, Elizabeth H., Holmboe, Eric S., Mattera, Jennifer A., Roumanis, Sarah A., Radford, Martha J., and Krumholz, Harlan M.

Subjects
Heart attack -- Drug therapy, Adrenergic beta blockers -- Health aspects, Hospitals -- Administration
Abstract

There are several factors that make some hospitals more likely to treat heart attack patients with beta blockers. They include having doctors on staff who advocate beta blocker use, and strong support for this position among other staff doctors and hospital administrators. Beta blockers can lower mortality rates from a heart attack.

Published
2001

40. Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease

Author

Emdin, Connor A., Khera, Amit V., Chaffin, Mark, Klarin, Derek, Natarajan, Pradeep, Aragam, Krishna, Haas, Mary, Bick, Alexander, Zekavat, Seyedeh M., Nomura, Akihiro, Ardissino, Diego, Wilson, James G., Schunkert, Heribert, McPherson, Ruth, Watkins, Hugh, Elosua, Roberto, Bown, Matthew J., Samani, Nilesh J., Baber, Usman, Erdmann, Jeanette, Gupta, Namrata, Danesh, John, Chasman, Daniel, Ridker, Paul, Denny, Joshua, Bastarache, Lisa, Lichtman, Judith H., D’Onofrio, Gail, Mattera, Jennifer, Spertus, John A., Sheu, Wayne H.-H., Taylor, Kent D., Psaty, Bruce M., Rich, Stephen S., Post, Wendy, Rotter, Jerome I., Chen, Yii-Der Ida, Krumholz, Harlan, Saleheen, Danish, Gabriel, Stacey, and Kathiresan, Sekar

Abstract

Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency < 5%) pLOF variant-phenotype associations. pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, in the gene IL33 against asthma and allergic disease, and in the gene IFIH1 against hypothyroidism. In the gene PDE3B, pLOF variants associate with elevated height, improved body fat distribution and protection from coronary artery disease. Our findings prioritize genes for which pharmacologic mimics of pLOF variants may lower risk for disease.

Published
2018
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44. Variation in Recovery

Author

Lichtman, Judith H., primary, Lorenze, Nancy P., additional, D'Onofrio, Gail, additional, Spertus, John A., additional, Lindau, Stacy T., additional, Morgan, Thomas M., additional, Herrin, Jeph, additional, Bueno, Héctor, additional, Mattera, Jennifer A., additional, Ridker, Paul M., additional, and Krumholz, Harlan M., additional

Published
2010
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45. An Administrative Claims Measure Suitable for Profiling Hospital Performance on the Basis of 30-Day All-Cause Readmission Rates Among Patients With Heart Failure

Author

Keenan, Patricia S., primary, Normand, Sharon-Lise T., additional, Lin, Zhenqiu, additional, Drye, Elizabeth E., additional, Bhat, Kanchana R., additional, Ross, Joseph S., additional, Schuur, Jeremiah D., additional, Stauffer, Brett D., additional, Bernheim, Susannah M., additional, Epstein, Andrew J., additional, Wang, Yongfei, additional, Herrin, Jeph, additional, Chen, Jersey, additional, Federer, Jessica J., additional, Mattera, Jennifer A., additional, Wang, Yun, additional, and Krumholz, Harlan M., additional

Published
2008
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48. Achieving Rapid Door-To-Balloon Times

Author

Bradley, Elizabeth H., primary, Curry, Leslie A., additional, Webster, Tashonna R., additional, Mattera, Jennifer A., additional, Roumanis, Sarah A., additional, Radford, Martha J., additional, McNamara, Robert L., additional, Barton, Barbara A., additional, Berg, David N., additional, and Krumholz, Harlan M., additional

Published
2006
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49. Achieving Door-to-Balloon Times That Meet Quality Guidelines

Author

Bradley, Elizabeth H., primary, Roumanis, Sarah A., additional, Radford, Martha J., additional, Webster, Tashonna R., additional, McNamara, Robert L., additional, Mattera, Jennifer A., additional, Barton, Barbara A., additional, Berg, David N., additional, Portnay, Edward L., additional, Moscovitz, Harry, additional, Parkosewich, Janet, additional, Holmboe, Eric S., additional, Blaney, Martha, additional, and Krumholz, Harlan M., additional

Published
2005
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