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Article ; Online: Genome-Wide Association Study of Pelvic Organ Prolapse Using the Michigan Genomics Initiative.

Cox, Caroline K / Pandit, Anita / Zawistowski, Matthew / Dutta, Diptavo / Narla, Goutham / Swenson, Carolyn W

Female pelvic medicine & reconstructive surgery

2021 Volume 27, Issue 8, Page(s) 502–506

Abstract: Objectives: The aim of this study was to (1) replicate previously identified genetic variants significantly associated with pelvic organ prolapse and (2) identify new genetic variants associated with pelvic organ prolapse using a genome-wide association ...

Abstract	Objectives: The aim of this study was to (1) replicate previously identified genetic variants significantly associated with pelvic organ prolapse and (2) identify new genetic variants associated with pelvic organ prolapse using a genome-wide association study. Methods: Using our institution's database linking genetic and clinical data, we identified 1,329 women of European ancestry with an International Classification of Diseases, Ninth Revision (ICD-9)/ICD-10 code for prolapse, 767 of whom also had Current Procedural Terminology (CPT)/ICD-9/ICD-10 procedure codes for prolapse surgery, and 16,383 women of European ancestry older than 40 years without a prolapse diagnosis code as controls. Patients were genotyped using the Illumina HumanCoreExome chip and imputed to the Haplotype Reference Consortium. We tested 20 million single nucleotide polymorphisms (SNPs) for association with pelvic organ prolapse adjusting for relatedness, age, chip version, and 4 principal components. We compared our results with 18 previously identified genome-wide significant SNPs from the UK Biobank, Commun Biol (2020;3:129), and Obstet Gynecol (2011;118:1345-1353). Results: No variants achieved genome-wide significance (P = 5 × 10-8). However, we replicated 4 SNPs with biologic plausibility at nominal significance (P ≤ 0.05): rs12325192 (P = 0.002), rs9306894 (P = 0.05), rs1920568 (P = 0.034), and rs1247943 (P = 0.041), which were all intergenic and nearest the genes SALL1, GDF7, TBX5, and TBX5, respectively. Conclusions: Our replication of 4 biologically plausible previously reported SNPs provides further evidence for a genetic contribution to prolapse, specifically that rs12325192, rs9306894, rs1920568, and rs1247943 may contribute to susceptibility for prolapse. These and previously reported associations that have not yet been replicated should be further explored in larger, more diverse cohorts, perhaps through meta-analysis.
MeSH term(s)	Adult ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Humans ; Michigan ; Middle Aged ; Pelvic Organ Prolapse/genetics ; Pelvic Organ Prolapse/surgery ; Polymorphism, Single Nucleotide ; White People
Language	English
Publishing date	2021-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2542707-6
ISSN	2154-4212 ; 2151-8378
ISSN (online)	2154-4212
ISSN	2151-8378
DOI	10.1097/SPV.0000000000001075
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Article ; Online: Nightmares share genetic risk factors with sleep and psychiatric traits.

Ollila, Hanna M / Sinnott-Armstrong, Nasa / Kantojärvi, Katri / Broberg, Martin / Palviainen, Teemu / Jones, Samuel / Ripatti, Vili / Pandit, Anita / Rong, Robin / Kristiansson, Kati / Sandman, Nils / Valli, Katja / Hublin, Christer / Ripatti, Samuli / Widen, Elisabeth / Kaprio, Jaakko / Saxena, Richa / Paunio, Tiina

Translational psychiatry

2024 Volume 14, Issue 1, Page(s) 123

Abstract: Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional ... ...

Abstract	Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e-06), depressive (rg = 0.562, p = 1.282e-07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e-07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual's liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.
MeSH term(s)	Humans ; Dreams/psychology ; Sleep Initiation and Maintenance Disorders/genetics ; Genome-Wide Association Study ; Anxiety Disorders ; Risk Factors
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-023-02637-6
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Article: Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.

Douville, Nicholas J / Larach, Daniel B / Lewis, Adam / Bastarache, Lisa / Pandit, Anita / He, Jing / Heung, Michael / Mathis, Michael / Wanderer, Jonathan P / Kheterpal, Sachin / Surakka, Ida / Kertai, Miklos D

Frontiers in genetics

2023 Volume 14, Page(s) 1094908

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-04-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1094908
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Article ; Online: The Michigan Genomics Initiative: A biobank linking genotypes and electronic clinical records in Michigan Medicine patients.

Zawistowski, Matthew / Fritsche, Lars G / Pandit, Anita / Vanderwerff, Brett / Patil, Snehal / Schmidt, Ellen M / VandeHaar, Peter / Willer, Cristen J / Brummett, Chad M / Kheterpal, Sachin / Zhou, Xiang / Boehnke, Michael / Abecasis, Gonçalo R / Zöllner, Sebastian

Cell genomics

2023 Volume 3, Issue 2, Page(s) 100257

Abstract: Biobanks of linked clinical patient histories and biological samples are an efficient strategy to generate large cohorts for modern genetics research. Biobank recruitment varies by factors such as geographic catchment and sampling strategy, which affect ... ...

Abstract	Biobanks of linked clinical patient histories and biological samples are an efficient strategy to generate large cohorts for modern genetics research. Biobank recruitment varies by factors such as geographic catchment and sampling strategy, which affect biobank demographics and research utility. Here, we describe the Michigan Genomics Initiative (MGI), a single-health-system biobank currently consisting of >91,000 participants recruited primarily during surgical encounters at Michigan Medicine. The surgical enrollment results in a biobank enriched for many diseases and ideally suited for a disease genetics cohort. Compared with the much larger population-based UK Biobank, MGI has higher prevalence for nearly all diagnosis-code-based phenotypes and larger absolute case counts for many phenotypes. Genome-wide association study (GWAS) results replicate known findings, thereby validating the genetic and clinical data. Our results illustrate that opportunistic biobank sampling within single health systems provides a unique and complementary resource for exploring the genetics of complex diseases.
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2023.100257
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Article ; Online: The phenotype-genotype reference map: Improving biobank data science through replication.

Bastarache, Lisa / Delozier, Sarah / Pandit, Anita / He, Jing / Lewis, Adam / Annis, Aubrey C / LeFaive, Jonathon / Denny, Joshua C / Carroll, Robert J / Altman, Russ B / Hughey, Jacob J / Zawistowski, Matthew / Peterson, Josh F

American journal of human genetics

2023 Volume 110, Issue 9, Page(s) 1522–1533

Abstract: Population-scale biobanks linked to electronic health record data provide vast opportunities to extend our knowledge of human genetics and discover new phenotype-genotype associations. Given their dense phenotype data, biobanks can also facilitate ... ...

Abstract	Population-scale biobanks linked to electronic health record data provide vast opportunities to extend our knowledge of human genetics and discover new phenotype-genotype associations. Given their dense phenotype data, biobanks can also facilitate replication studies on a phenome-wide scale. Here, we introduce the phenotype-genotype reference map (PGRM), a set of 5,879 genetic associations from 523 GWAS publications that can be used for high-throughput replication experiments. PGRM phenotypes are standardized as phecodes, ensuring interoperability between biobanks. We applied the PGRM to five ancestry-specific cohorts from four independent biobanks and found evidence of robust replications across a wide array of phenotypes. We show how the PGRM can be used to detect data corruption and to empirically assess parameters for phenome-wide studies. Finally, we use the PGRM to explore factors associated with replicability of GWAS results.
MeSH term(s)	Humans ; Biological Specimen Banks ; Data Science ; Phenomics ; Phenotype ; Genotype
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2023.07.012
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Article: ASSESSING SELECTION BIAS IN REGRESSION COEFFICIENTS ESTIMATED FROM NONPROBABILITY SAMPLES WITH APPLICATIONS TO GENETICS AND DEMOGRAPHIC SURVEYS.

West, Brady T / Little, Roderick J / Andridge, Rebecca R / Boonstra, Philip S / Ware, Erin B / Pandit, Anita / Alvarado-Leiton, Fernanda

The annals of applied statistics

2021 Volume 15, Issue 3, Page(s) 1556–1581

Abstract: Selection bias is a serious potential problem for inference about relationships of scientific interest based on samples without well-defined probability sampling mechanisms. Motivated by the potential for selection bias in: (a) estimated relationships of ...

Abstract	Selection bias is a serious potential problem for inference about relationships of scientific interest based on samples without well-defined probability sampling mechanisms. Motivated by the potential for selection bias in: (a) estimated relationships of polygenic scores (PGSs) with phenotypes in genetic studies of volunteers and (b) estimated differences in subgroup means in surveys of smartphone users, we derive novel measures of selection bias for estimates of the coefficients in linear and probit regression models fitted to nonprobability samples, when aggregate-level auxiliary data are available for the selected sample and the target population. The measures arise from normal pattern-mixture models that allow analysts to examine the sensitivity of their inferences to assumptions about nonignorable selection in these samples. We examine the effectiveness of the proposed measures in a simulation study and then use them to quantify the selection bias in: (a) estimated PGS-phenotype relationships in a large study of volunteers recruited via Facebook and (b) estimated subgroup differences in mean past-year employment duration in a nonprobability sample of low-educated smartphone users. We evaluate the performance of the measures in these applications using benchmark estimates from large probability samples.
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2376910-5
ISSN	1941-7330 ; 1932-6157
ISSN (online)	1941-7330
ISSN	1932-6157
DOI	10.1214/21-aoas1453
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Article ; Online: Hospital Quality and Performance of a Complex Surgical Procedure after Traumatic Digit Amputation.

Swiatek, Peter R / Pandit, Anita / Chung, Kevin C / Mahmoudi, Elham

Plastic and reconstructive surgery

2016 Volume 138, Issue 1, Page(s) 141–151

Abstract: Background: Traumatic digit amputations are prevalent injuries that have long-term disabling consequences. Although replantation after traumatic digit amputation is a complex procedure, the aesthetic, functional, and long-term economic benefits of ... ...

Abstract	Background: Traumatic digit amputations are prevalent injuries that have long-term disabling consequences. Although replantation after traumatic digit amputation is a complex procedure, the aesthetic, functional, and long-term economic benefits of replantation render it preferable to revision amputation when clinically indicated. The authors adapted the Donabedian quality-of-care conceptual framework to examine the association between hospital outcome quality measured by observed-to-expected mortality ratio and the treatment received after traumatic digit amputation. The authors hypothesized that the probability of undergoing replantation is higher in hospitals with lower observed-to-expected mortality ratios. Methods: Data from 106 qualified Level I and II trauma centers included in the 2007 to 2012 National Trauma Data Bank were used to estimate hospital-specific observed-to-expected mortality ratio. The authors then used a two-level logistic hierarchical model, adjusting for patient, clinical, and hospital characteristics, to examine whether observed-to-expected mortality ratio, as one of the commonly used hospital quality measures, is a predictor of the treatment received for 4169 patients with traumatic digit amputation. Results: Compared with trauma centers with high observed-to-expected mortality ratios, the probability of undergoing replantation was substantially higher in trauma centers with low observed-to-expected mortality ratios (OR, 5.09; 95 percent CI, 2.51 to 10.30; p < 0.001). Seeking care at hospitals with more than 400 beds increased the probability of digit replantation (OR, 2.08; 95 percent CI, 1.08 to 4.01; p = 0.029). Having no insurance decreased the odds of undergoing replantation (OR, 0.70; 95 percent CI, 0.53 to 0.91; p = 0.009). Conclusions: Hospital observed-to-expected mortality ratio was the greatest predictor of undergoing replantation after digit amputation injury. The observed-to-expected mortality ratio, as an outcome measure of hospital quality, is an important predictor of the treatment received.
MeSH term(s)	Adolescent ; Adult ; Aged ; Amputation, Traumatic/surgery ; Female ; Finger Injuries/surgery ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Quality Indicators, Health Care ; Reoperation ; Replantation/methods ; Retrospective Studies ; Trauma Centers/standards ; United States ; Young Adult
Language	English
Publishing date	2016-02-07
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0000000000002287
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Article ; Online: Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients.

Larach, Daniel B / Lewis, Adam / Bastarache, Lisa / Pandit, Anita / He, Jing / Sinha, Anik / Douville, Nicholas J / Heung, Michael / Mathis, Michael R / Mosley, Jonathan D / Wanderer, Jonathan P / Kheterpal, Sachin / Zawistowski, Matthew / Brummett, Chad M / Siew, Edward D / Robinson-Cohen, Cassianne / Kertai, Miklos D

BMC nephrology

2022 Volume 23, Issue 1, Page(s) 339

Abstract: Background: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of ... ...

Abstract	Background: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. Methods: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. Results: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. Conclusion: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.
MeSH term(s)	Male ; Adult ; Humans ; Female ; Genome-Wide Association Study ; Retrospective Studies ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/epidemiology ; Acute Kidney Injury/genetics ; Glomerular Filtration Rate ; Risk Factors ; Postoperative Complications/genetics ; Postoperative Complications/epidemiology
Language	English
Publishing date	2022-10-21
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-022-02964-8
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Article ; Online: The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities.

Beesley, Lauren J / Salvatore, Maxwell / Fritsche, Lars G / Pandit, Anita / Rao, Arvind / Brummett, Chad / Willer, Cristen J / Lisabeth, Lynda D / Mukherjee, Bhramar

Statistics in medicine

2019 Volume 39, Issue 6, Page(s) 773–800

Abstract: Biobanks linked to electronic health records provide rich resources for health-related research. With improvements in administrative and informatics infrastructure, the availability and utility of data from biobanks have dramatically increased. In this ... ...

Abstract	Biobanks linked to electronic health records provide rich resources for health-related research. With improvements in administrative and informatics infrastructure, the availability and utility of data from biobanks have dramatically increased. In this paper, we first aim to characterize the current landscape of available biobanks and to describe specific biobanks, including their place of origin, size, and data types. The development and accessibility of large-scale biorepositories provide the opportunity to accelerate agnostic searches, expedite discoveries, and conduct hypothesis-generating studies of disease-treatment, disease-exposure, and disease-gene associations. Rather than designing and implementing a single study focused on a few targeted hypotheses, researchers can potentially use biobanks' existing resources to answer an expanded selection of exploratory questions as quickly as they can analyze them. However, there are many obvious and subtle challenges with the design and analysis of biobank-based studies. Our second aim is to discuss statistical issues related to biobank research such as study design, sampling strategy, phenotype identification, and missing data. We focus our discussion on biobanks that are linked to electronic health records. Some of the analytic issues are illustrated using data from the Michigan Genomics Initiative and UK Biobank, two biobanks with two different recruitment mechanisms. We summarize the current body of literature for addressing these challenges and discuss some standing open problems. This work complements and extends recent reviews about biobank-based research and serves as a resource catalog with analytical and practical guidance for statisticians, epidemiologists, and other medical researchers pursuing research using biobanks.
MeSH term(s)	Biological Specimen Banks ; Electronic Health Records ; Genomics ; Michigan ; Research Design
Language	English
Publishing date	2019-12-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.8445
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Article ; Online: Multi-ancestry meta-analysis identifies 5 novel loci for ischemic stroke and reveals heterogeneity of effects between sexes and ancestries.

Cell genomics

2023 Volume 3, Issue 8, Page(s) 100345

Abstract: Stroke is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, possibly due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ... ...

Abstract	Stroke is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, possibly due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetics of ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI) and further combined the results with previously published MegaStroke. Five novel loci for ischemic stroke (
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2023.100345
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