Population Management of Post Bariatric Surgery Patients to Prevent Micronutrient Deficiencies
Bariatric surgery is the most effective long-term treatment for severe obesity. However, post-bariatric surgery patients develop vitamin malabsorption due to altered anatomy that can lead to micronutrient deficiencies. The overall goal of this study is to investigate whether the creation of a population management program specifically developed for patients who underwent bariatric surgery can improve achieving meaningful long-term compliance and postoperative outcomes. We hypothesize that population outreach significantly improves compliance in post-bariatric surgery patients, leading to a reduction in micronutrient deficiencies and associated complications.
Investigator: Choquet, Helene
Funder: TPMG Delivery Science Projects Program
Targeted metabolomics for early pregnancy prediction of gestational diabetes mellitus
This study will apply a targeted metabolomics approach to the prediction of gestational diabetes from a single blood sample collected in the first trimester of pregnancy and stored for the Research Program on Genes, Environment and Health pregnancy cohort study, which recruited 24,000 pregnant participants during early pregnancy through delivery within Kaiser Permanente Northern California. This large racially and ethnically diverse pregnancy cohort, with stored biospecimens, and clinical data and perinatal health outcomes from electronic health records, provides an excellent opportunity to conduct a nested case-control study among women without prior diabetes to identify a metabolite profile predicting subsequent gestational diabetes diagnosis during mid-gestation. This study will involve a specialized targeted metabolomics approach that can reveal risk of gestational diabetes significantly sooner than conventional tests.
Investigator: Gunderson, Erica
Funder: University of Toronto
Prioritizing diversity in polygenic risk prediction of primary open-angle glaucoma
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss, yet much of the genetic risk remains unaccounted for, especially in African-Americans, who have a higher risk for developing POAG. This proposal aims to bring together the largest African-descent glaucoma datasets in the world to identify novel POAG loci that may be specific to people of African descent through both genome-wide association studies and admixture mapping. We will also develop and test ancestry-specific polygenic risk scores in African-descent populations.
Investigator: Choquet, Helene
Funder: National Eye Institute
The Role of Genetic and Non-Genetic Factors and Causal Mechanisms Underlying Cataract Susceptibility For Risk Prediction
Cataract is a leading cause of blindness and a major cause of impaired vision worldwide. The overall objective of this study is to better understand the role of genetic and non-genetic factors and causal mechanisms underlying the etiology of cataract and develop a prediction tool to facilitate risk-stratified screening for cataract. This study has 3 major aims: 1) to evaluate whether glaucoma, myopic refractive error, diabetes, high blood pressure, high BMI, cigarette smoking, or alcohol consumption, and other non-genetic factors are causal risk factors of cataract; 2) to develop risk prediction models of cataract susceptibility based on genetic and non-genetic risk factors; and 3) to determine the function (in the lens tissue) of novel candidate genes prioritized within genetic loci associated with cataract.
Investigator: Choquet, Helene
Funder: National Eye Institute
Genetic and non-genetic factors affecting weight loss variability after bariatric surgery
Bariatric surgery is currently the most effective long-term treatment for severe obesity. However, inter-individual variability in surgery outcomes has been observed, particularly in relation to postoperative weight loss. This study aims to assess the contribution of genetic and non-genetic factors to such inter-individual variability by leveraging a large and ethnically diverse cohort with longitudinal electronic health record data. Study findings could help to develop predictive risk scores for outcomes of bariatric surgery based on genetic information along with other demographic and clinical factors. In future clinical practice, predictive risk scores could help patients be realistic about the outcomes of bariatric surgery and guide treatment strategies for patients with severe obesity.
Investigator: Choquet, Helene
Funder: Northern California Community Benefit Programs
Identification of genetic loci and pathways underlying hidradenitis suppurativa risk
Hidradenitis suppurativa (also named: acne inversa) is a chronic inflammatory skin condition that causes painful lumps to form under the skin usually in areas where skin rubs together such as in the armpits, groin, buttocks and under breasts. The overall scientific objective of this study is to identify and validate genetic factors associated with the risk of hidradenitis suppurativa, with the long-term goal of uncovering new therapeutic targets.
Investigator: Choquet, Helene
Funder: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Statin Treatment and Incident Alzheimer’s Disease and Related Dementias in a Large, Multi-ethnic Health Plan
The study will assess the effects of statin treatment on risk of Alzheimer’s disease and related dementias, controlling for potential confounding and examining potential mediating factors among Kaiser Permanente Northern California members during the years 1996 to 2020. A second aim will examine the role of genetic factors in the association of statin treatment and dementia risk in a cohort of genotyped KPNC members.
Investigator: Schaefer, Catherine
Funder: National Institute on Aging
Bipolar Disease and Parkinson’s Disease
This study, along with a parallel effort at the University of California, San Francisco, will focus on the relationship between bipolar disease and Parkinson’s disease.
Investigator: Van Den Eeden, Stephen
Funder: Michael J. Fox Foundation
The Role of Genetic Risk Factors in Keratinocyte Carcinoma Susceptibility
The goal of this proposal is to identify genetic loci that affect the risk of keratinocyte carcinoma, examine how environmental risk factors influence genetic risk, and determine whether these loci act to influence the risk of basal cell carcinoma, squamous cell carcinoma, or both.
Investigator: Choquet, Helene; Asgari, Maryam
Funder: National Cancer Institute
Genetics at an Extreme: An Efficient Genomic Study of Individuals with Clinically Severe Major Depression Receiving ECT
This
study brings together investigators from around the world to carry out a
genetics study of severe major depressive disorder (MDD) treated with
electroconvulsive therapy (ECT). The National Network of Depression Centers
and allied centers in the U.S. will carry out a genetics study that will
enroll 25,000 patients receiving ECT for severe MDD. The centers will also
carry out a genome-wide association study comparing these 25,000 cases with
50,000 non-depressed and tightly matched previously collected controls. They
will also carry out a genome-wide association study of response to ECT in the
10,000 patients with prospective follow-up data. Analysis will consider changes in measures
of depression and cognitive function, test for genetic variances associated
with these responses, and examine prediction models.
Investigator: Schaefer, Catherine
Funder: National Institute of Mental Health
Alzheimer’s Disease and Related Dementias in a Diverse Cohort of Asian Americans
This study considers the extent to which immigration history, social factors, cardiometabolic health, and genetic factors contribute to heterogeneity in dementia incidence between Asian American subgroups and between Asian Americans and whites.
Investigator: Jorgenson, Eric
Funder: National Institute on Aging
ICLIC-MS for Enhancing Outcomes Research and Clinical Care in Multiple Sclerosis
The goal of this project is 1) to collect longitudinal measures of cognitive function, quality of life, and physical disability on a multi-ethnic sample of 3,000 individuals with multiple sclerosis (MS), using a web-based interface, Clinical and Longitudinal Information Collection for MS (ICLIC-MS); 2) to use these data in conjunction with already-collected data on genetic and environmental factors that affect risk of MS to better understand factors that influence progression of MS; and 3) to develop a report to provide information to treating neurologists about changes in cognitive function, quality of life, and physical disability that can be used to inform treatment of MS.
Investigator: Schaefer, Catherine
Funder: National Institute of Nursing Research
Closing the Gap Between Observational Research and Randomized Trials for Prevention of Alzheimer‘s Disease and Dementia
Observational studies should have a core role in justifying and guiding the development of randomized controlled trials, but to date observational research and trials on Alzheimer’s disease prevention are not closely aligned. Observational and randomized studies nearly always answer different questions, even when nominally addressing similar topics. Integration across heterogeneous observational data sources will be necessary to provide the sample size, diversity, and variety of measurements to provide such specificity, but currently, we do not have systematic tools to combine evidence from heterogeneous data sources to guide trial design. This proposal builds on Robins g-formula–based methods for counterfactual simulations and takes advantage of recent critical advances in causal methods for data integration, based on Pearls d-separation criteria for transportability.
Investigator: Jorgenson, Eric
Funder: National Institute on Aging
Investigating the Effects of KIR and HLA Gene Polymorphisms on Psoriasis
The goal of this project is to investigate the effects of genetic polymorphisms in the KIR and HLA genes on psoriasis and psoriatic arthritis.
Investigator: Jorgenson, Eric
Funder: University of California, Los Angeles
Population-Based Pharmacogenomic Assessment of QT Prolongation
Cardiotoxicity of commonly prescribed medications, typically assessed by electrocardiographic features such as prolongation of the QT interval, has regulatory effects and is associated with potentially fatal outcomes. This project aims to advance understanding of the genetic basis for drug cardiotoxicity and its downstream consequences by leveraging the extensive data resources of the Kaiser Permanente Northern California Research Program on Genes, Environment and Health (RPGEH), and the ability to link these data to other health plan databases, namely Kaiser Permanente Northern California’s pharmacy, electrocardiogram, and outpatient/inpatient utilization databases. Longitudinal analyses of the QT interval over up to 20 years will be conducted in the large and ethnically diverse Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort of the RPGEH. Genetic loci that influence adverse drug reactions will be identified and characterized, and the associated biological pathways and tissues will be investigated. This study will also examine: a) genetic predictors of adverse outcomes (e.g., ventricular arrhythmias and Torsade de Pointes), b) whether the identified gene-by-drug interactions are associated with these adverse outcomes, and c) degree of mediation by QTc prolongation.
Investigator: Iribarren, Carlos
Funder: National Heart, Lung, and Blood Institute
Maternal Inflammation during Pregnancy and Neurodevelopmental Disorders
This study will utilize the Pregnancy Cohort from the Kaiser Permanente Northern California Research Program on Genes, Environment and Health to characterize the maternal immune profile over pregnancy and evaluate whether there are specific longitudinal patterns that are associated with neurodevelopmental outcomes in the offspring. The project will identify factors that are associated with longitudinal patterns of maternal immune markers over pregnancy and examine whether there is variability in risk factors across different neurodevelopmental outcomes. Factors to be examined include maternal demographic, lifestyle, clinical, and genetic factors.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development
Germline and Tumor Genomic Analyses of Breast Cancer in Latinas
This project expands a consortium of studies examining germline genetic mutations in breast cancer risk in Latinas. It builds on a study that will include approximately 550 Latina women with breast cancer in the Pathways Study; genetic data from Latina women without breast cancer will be contributed from Kaiser Permanente Northern California’s Research Program on Genes, Environment and Health. Led by Susan Neuhausen, PhD, of City of Hope, and Elad Ziv, MD, of UC San Francisco, this project further incorporates Latina cases and controls from studies led by Dr. Neuhausen. While this project includes investigation of tumor DNA, Pathways Study and Kaiser Permanente Northern California participants will not be included in that aspect.
Investigator: Kushi, Lawrence
Funder: National Cancer Institute
Genetic Etiology of Abdominal Hernia Susceptibility
The objective of this project is to investigate the genetic mechanisms that drive the development of abdominal hernias. This study has three major aims: 1) to investigate the shared and individual genetic risks of different types of abdominal hernia, 2) to examine the genetic risk factors underlying recurrence of hernias in individual patients, and 3) to investigate the genetic pathways and biological mechanisms through which abdominal hernia risk loci act.
Investigator: Choquet, Helene
Funder: National Institute of Diabetes and Digestive and Kidney Diseases
The Bipolar Sequencing Consortium for Combined Analyses and Follow-Up
The International Bipolar Sequencing Consortium brings together whole-genome and exome sequence data from multiple case-control and family studies of bipolar disorder for the purpose of investigating the genetic architecture of this condition. Data from multiple institutions and studies will be combined and harmonized to examine associations of genetic variation with bipolar disorder. De-identified exome sequence data from 483 individuals with bipolar disorder and 483 matched controls will be provided from the Multi-Ethnic Genome-wide Association Study of Bipolar Disorder at Kaiser Permanente Northern California, which will participate in analyses of the harmonized dataset from all study sites.
Investigator: Schaefer, Catherine
Funder: National Institute of Mental Health
The Role of Refractive Error in the Etiology of Glaucoma
The specific aims of this study are to: 1) Determine whether refractive error predicts the development of glaucoma due to direct effects or shared etiology, or both, by conducting a series of genetic analyses of the two conditions; and 2) Determine the contribution of refractive error (myopia) and relevant biological pathways in the development of glaucomatous neurodegeneration.
Investigator: Choquet, Helene
Funder: National Eye Institute
Cognitive Function and Physical Disability in White, Black and Hispanic MS Patients
Cognitive impairment, physical disability and progressive disease are common but understudied clinical outcomes that substantially impact quality of life for individuals with multiple sclerosis (MS). Systematic assessment of cognitive function, disability and progression is neither routinely performed, nor results captured electronically, for most MS patients undergoing medical care. To help address this gap, we have recently developed and validated a new guided, web-based interface (ICLIC-MS) for longitudinal data collection of MS-validated measures for these important outcomes and other symptoms. We will recruit and collect comprehensive data on cognitive function, physical disability and disease progression over three years from a multi-ethnic cohort of 600 individuals with confirmed MS or clinically isolated syndrome (CIS). The study will be nested in the Kaiser Permanente (KP) MS Research Program which is part of the KP Medical Care Program in the Northern California Region.
Investigator: Schaefer, Catherine
Funder: National Multiple Sclerosis Society
Comprehensive Colorectal Cancer Risk Prediction to Inform Personalized Screening
The aims of this study are: 1) To build a comprehensive risk-prediction model for colorectal cancer and advanced adenoma in 45,000 colorectal tumors and 45,000 controls based on existing common and rare genome-wide genetic variants, demographic characteristics, and lifestyle and environmental risk factors. 2) To evaluate the risk-prediction models by calibrating and validating the models in the community-based RPGEH cohort and compare it with current screening guidelines and published risk prediction models. 3) To translate abstract risk prediction estimates into individually tailored recommendations that can be used in public health and clinical settings. We will use our developed absolute risk estimates to recommend age to start intervention and the type of screening modality. We will also incorporate a cost-benefit in the decision curve analysis to help clinical decision making.
Investigator: Corley, Douglas
Funder: National Cancer Institute
Susceptibility Genes for Erectile Dysfunction
This Multi-PI grant (H. Wessells, UW & S. Van Den Eeden KPNC) will 1) develop phenotyping algorithms, 2) examine genetic factors that affect risk, and 3) assess if these factors differentially affect subgroups (e.g., diabetic men, etc.). The study will use the eMerge Network and RPGEH populations.
Investigator: Van Den Eeden, Stephen
Funder: National Institute of Diabetes and Digestive and Kidney Diseases
Replication of PheWAS for TRPV4 Variant in Kaiser Permanente GERA Cohort
We will use the RPGEH GERA cohort to investigate associations of genetic variation (SNP genotypes) with several related conditions, including congestive heart failure, chronic kidney disease, and possibly related phenotypes. Our first objective will be to replicate findings of association of a specific genetic variant with a number of phenotypes, including congestive heart failure, pulmonary edema, and kidney disease. We will utilize the same phenotype definitions as in the original analysis, based on algorithmic extraction of electronic medical record data. In parallel, we will pursue our second and third objectives, which focus on a more in-depth analysis of the role of genome-wide variation in congestive heart failure and kidney disease. This will involve the development of deep phenotypes for these conditions that utilize extensive characterization of these conditions using KPNC electronic records.
Investigator: Schaefer, Catherine
Funder: GlaxoSmithKline PLC
Association between the Genomic Prostate Score and Metastatic Recurrence
The primary goal of the study is to confirm that the pre-specified Genomic Prostate Score (GPS) from biopsy tumor tissue predicts metastatic recurrence (MR) in patients diagnosed with localized prostate cancer and treated with radical prostatectomy. Prostate cancer-specific death (PCSD) will be evaluated as a secondary endpoint.
Investigator: Van Den Eeden, Stephen
PGRN Administration Coordination Hub
This is the Administrative Coordination Hub for the Pharmacogenomics Research Network (PGRN). The main areas of responsibility include meetings support, communications and coordination of nascent network collaborations.
Investigator: Jorgenson, Eric
Genome-Wide Study of Hearing Impairment
More than 25% of individuals over age 65 and 50% of individuals over age 80 suffer from varying levels of age-related hearing impairment (AHRI), and adults are losing hearing at earlier ages than in the past. There is strong evidence that both genetic and environmental factors play a role in AHRI. This is a genome-wide association study that is orders of magnitude larger than previous studies in a cohort of 100,000 individuals nested in the Kaiser Research Program on Genes, Environment, and Health. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these genetic factors impact AHRI, which may help identify individuals at greater risk. Understanding the genetic factors will also lead to better understanding of the underlying biological mechanisms of AHRI, which may improve potential treatments.
Investigator: Schaefer, Catherine
Funder: University of California, San Francisco, Project Grant
Grant Development Work for Molecular Assay in Prostate Cancer
The goal of the study is to perform a retrospective study to evaluate biomarkers predictive of aggressive disease using Florescence In Situ Hybridization (FISH) among men with histologically confirmed, clinically localized disease (T1c- T2c) under Active Surveillance (AS).
Investigator: Van Den Eeden, Stephen
Funder: Abbott Laboratories
BioBank Northern California – Regional
The KP Research Bank aims to recruit 280,000 members (200,000 in the general cohort, 30,000 in the cancer cohort, and 50,000 in the pregnancy cohort) total across all regions, to increase the overall Biobank collection to 500,000 (410,000 in the general cohort, 30,000 in the cancer cohort, and 60,000 in the pregnancy cohort). Members will be consented to provide a biospecimen and complete a survey. Regions will participate in the recruitment and other Research Bank-related efforts, including scientific, strategic and operational.
Investigator: Schaefer, Catherine
Funder: Kaiser Foundation Research Institute
