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Article ; Online: A comparison of confidence distribution approaches for rare event meta-analysis.

Zabriskie, Brinley N / Corcoran, Chris / Senchaudhuri, Pralay

2021 Volume 40, Issue 24, Page(s) 5276–5297

Abstract: Meta-analysis of rare event data has recently received increasing attention due to the challenging issues rare events pose to traditional meta-analytic methods. One specific way to combine information and analyze rare event meta-analysis data utilizes ... ...

Abstract	Meta-analysis of rare event data has recently received increasing attention due to the challenging issues rare events pose to traditional meta-analytic methods. One specific way to combine information and analyze rare event meta-analysis data utilizes confidence distributions (CDs). While several CD methods exist, no comparisons have been made to determine which method is best suited for homogeneous or heterogeneous meta-analyses with rare events. In this article, we review several CD methods: Fisher's classic P-value combination method, one that combines P-value functions, another that combines confidence intervals, and one that combines confidence log-likelihood functions. We compare these CD approaches, and we propose and compare variations of these methods to determine which method produces reliable results for homogeneous or heterogeneous rare event meta-analyses. We find that for homogeneous rare event data, most CD methods perform very well. On the other hand, for heterogeneous rare event data, there is a clear split in performance between some CD methods, with some performing very poorly and others performing reasonably well.
MeSH term(s)	Humans ; Likelihood Functions ; Research Design
Language	English
Publishing date	2021-07-04
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9125
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Article ; Online: A permutation-based approach for heterogeneous meta-analyses of rare events.

Zabriskie, Brinley N / Corcoran, Chris / Senchaudhuri, Pralay

Statistics in medicine

2021 Volume 40, Issue 25, Page(s) 5587–5604

Abstract: The increasingly widespread use of meta-analysis has led to growing interest in meta-analytic methods for rare events and sparse data. Conventional approaches tend to perform very poorly in such settings. Recent work in this area has provided options for ...

Abstract	The increasingly widespread use of meta-analysis has led to growing interest in meta-analytic methods for rare events and sparse data. Conventional approaches tend to perform very poorly in such settings. Recent work in this area has provided options for sparse data, but these are still often hampered when heterogeneity across the available studies differs based on treatment group. We propose a permutation-based approach based on conditional logistic regression that accommodates this common contingency, providing more reliable statistical tests when such patterns of heterogeneity are observed. We find that commonly used methods can yield highly inflated Type I error rates, low confidence interval coverage, and bias when events are rare and non-negligible heterogeneity is present. Our method often produces much lower Type I error rates and higher confidence interval coverage than traditional methods in these circumstances. We illustrate the utility of our method by comparing it to several other methods via a simulation study and analyzing an example data set, which assess the use of antibiotics to prevent acute rheumatic fever.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Bias ; Computer Simulation ; Humans ; Logistic Models
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9142
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Article ; Online: Interpreting Mini-Mental State Examination Performance in Highly Proficient Bilingual Spanish-English and Asian Indian-English Speakers: Demographic Adjustments, Item Analyses, and Supplemental Measures.

Milman, Lisa H / Faroqi-Shah, Yasmeen / Corcoran, Chris D / Damele, Deanna M

Journal of speech, language, and hearing research : JSLHR

2018 Volume 61, Issue 4, Page(s) 847–856

Abstract: Purpose: Performance on the Mini-Mental State Examination (MMSE), among the most widely used global screens of adult cognitive status, is affected by demographic variables including age, education, and ethnicity. This study extends prior research by ... ...

Abstract	Purpose: Performance on the Mini-Mental State Examination (MMSE), among the most widely used global screens of adult cognitive status, is affected by demographic variables including age, education, and ethnicity. This study extends prior research by examining the specific effects of bilingualism on MMSE performance. Method: Sixty independent community-dwelling monolingual and bilingual adults were recruited from eastern and western regions of the United States in this cross-sectional group study. Independent sample t tests were used to compare 2 bilingual groups (Spanish-English and Asian Indian-English) with matched monolingual speakers on the MMSE, demographically adjusted MMSE scores, MMSE item scores, and a nonverbal cognitive measure. Regression analyses were also performed to determine whether language proficiency predicted MMSE performance in both groups of bilingual speakers. Results: Group differences were evident on the MMSE, on demographically adjusted MMSE scores, and on a small subset of individual MMSE items. Scores on a standardized screen of language proficiency predicted a significant proportion of the variance in the MMSE scores of both bilingual groups. Conclusions: Bilingual speakers demonstrated distinct performance profiles on the MMSE. Results suggest that supplementing the MMSE with a language screen, administering a nonverbal measure, and/or evaluating item-based patterns of performance may assist with test interpretation for this population.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Independent Living ; Male ; Mental Status and Dementia Tests ; Middle Aged ; Multilingualism ; Young Adult
Language	English
Publishing date	2018-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1364086-0
ISSN	1558-9102 ; 1092-4388
ISSN (online)	1558-9102
ISSN	1092-4388
DOI	10.1044/2017_JSLHR-L-17-0021
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Article ; Online: Erratum to: "Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene Polymorphisms: The Cache County Memory Study".

Matyi, Joshua / Tschanz, JoAnn T / Rattinger, Gail B / Sanders, Chelsea / Vernon, Elizabeth K / Corcoran, Chris / Kauwe, John S K / Buhusi, Mona

The journals of gerontology. Series A, Biological sciences and medical sciences

2018 Volume 73, Issue 3, Page(s) 311

Language	English
Publishing date	2018-01-16
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glx220
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Article ; Online: Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels.

Maxwell, Taylor J / Corcoran, Chris / Del-Aguila, Jorge L / Budde, John P / Deming, Yuetiva / Cruchaga, Carlos / Goate, Alison M / Kauwe, John S K

Alzheimer's research & therapy

2018 Volume 10, Issue 1, Page(s) 86

Abstract: Background: A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by- ... ...

Abstract	Background: A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G. Methods: We performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping was used to assess significance. Results: We found four significant tau/Aβ42 rQTL from three unique locations and six ptau/Aβ42 rQTL from five unique locations. G×G screens with these rQTL produced four significant G×G interactions (one Aβ42, two ptau, and one tau) with four rQTL where each second locus was from a unique location. On follow-up, rs1036819 and rs74025622 were associated with Alzheimer's disease (AD) case/control status; rs15205 and rs79099429 were associated with rate of decline. Conclusions: The two most significant rQTL (rs8027714 and rs1036819) for ptau/Aβ42 are on different chromosomes and both are strong hits for pelvic organ prolapse. While diseases of the nervous system can cause pelvic organ prolapse, it is unlikely related to the ptau/Aβ42 relationship but may suggest that these two loci share a pathway. In addition to a ptau/Aβ42 rQTL and association with AD case/control status, rs1036819 is a strong rQTL for case/control status/Aβ42 and for tau/Aβ42. It resides in the ZFAT gene, which is related to autoimmune thyroid disease. For tau, rs9817620 interacts with the tau/Aβ42 rQTL rs74025622. It is in the CHL1 gene, which is a neural cell adhesion molecule and may be involved in signal transduction pathways. CHL1 is related to BACE1, which is a β-secretase enzyme that initiates production of the β-amyloid peptide involved in AD and is a primary drug target. Overall, there are numerous loci that affect the relationship between these important AD endophenotypes and some are due to interactions with other loci. Some affect the risk of AD and/or rate of progression.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/cerebrospinal fluid ; Amyloid beta-Peptides/genetics ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Peptide Fragments/cerebrospinal fluid ; Peptide Fragments/genetics ; Phosphorylation ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; tau Proteins/cerebrospinal fluid ; tau Proteins/genetics
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; MAPT protein, human ; Peptide Fragments ; amyloid beta-protein (1-42) ; tau Proteins
Language	English
Publishing date	2018-08-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-018-0410-y
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Article ; Online: Nutritional Status is Associated With Severe Dementia and Mortality: The Cache County Dementia Progression Study.

Sanders, Chelsea L / Wengreen, Heidi J / Schwartz, Sarah / Behrens, Stephanie J / Corcoran, Chris / Lyketsos, Constantine G / Tschanz, JoAnn T

Alzheimer disease and associated disorders

2018 Volume 32, Issue 4, Page(s) 298–304

Abstract: Purpose: Studies have reported faster cognitive/functional decline in persons with dementia (PWD) with malnutrition. We investigated whether baseline nutritional status predicted severe dementia and mortality in a population-based sample.: Patients: ... ...

Abstract	Purpose: Studies have reported faster cognitive/functional decline in persons with dementia (PWD) with malnutrition. We investigated whether baseline nutritional status predicted severe dementia and mortality in a population-based sample. Patients: A maximum of 300 PWD were assessed annually for up to 8.6 years. Methods: Nutritional status was assessed using a modified Mini-Nutritional Assessment (mMNA). Severe dementia was defined as: "severe" rating on the Clinical Dementia Rating or Mini-Mental State Examination score ≤10. Using Cox proportional hazards models, we examined the association between baseline mMNA score (or its subcomponents) with each outcome. Covariates included demographics; dementia onset age, type, and duration; APOE genotype; and residency with caregiver. Results: Compared with "well-nourished," "malnourished" PWD had 3-4 times the hazard of severe dementia [hazard ratio (HR), 4.31; P=0.014] and death (HR, 3.04; P<0.001). Those "at risk for malnutrition" had twice the hazard of severe dementia (HR, 1.98; P=0.064) and 1.5 times the hazard of death (HR, 1.46; P=0.015). mMNA subcomponents of food group intake, weight loss, body mass index, mobility, health status, protein consumption, and mid-arm circumference predicted one or both outcomes. Conclusions: Nutritional status is an important predictor of clinical outcomes in dementia and may provide an avenue for intervention.
MeSH term(s)	Activities of Daily Living ; Aged, 80 and over ; Dementia/epidemiology ; Dementia/metabolism ; Disease Progression ; Female ; Humans ; Incidence ; Male ; Mental Status and Dementia Tests ; Mortality/trends ; Nutritional Status/physiology ; Surveys and Questionnaires ; Utah/epidemiology
Language	English
Publishing date	2018-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1002700-2
ISSN	1546-4156 ; 0893-0341
ISSN (online)	1546-4156
ISSN	0893-0341
DOI	10.1097/WAD.0000000000000274
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Article ; Online: Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene Polymorphisms: The Cache County Memory Study.

Matyi, Joshua / Tschanz, JoAnn T / Rattinger, Gail B / Sanders, Chelsea / Vernon, Elizabeth K / Corcoran, Chris / Kauwe, John S K / Buhusi, Mona

The journals of gerontology. Series A, Biological sciences and medical sciences

2017 Volume 72, Issue 12, Page(s) 1607–1613

Abstract: Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex ... ...

Abstract	Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex differences in risk. We examined four single-nucleotide polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415, rs2289656, rs2072446) and risk for AD by sex in a population-based sample of older adults. Three thousand four hundred and ninety-nine individuals without dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female] underwent dementia screening and assessment over four triennial waves. Cox regression was used to examine time to AD or right censoring for each SNP. Female carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93, 95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61% lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level significance (p = .07). The association between certain neurotrophin gene polymorphisms and AD differs by sex and may explain inconsistent findings in the literature.
MeSH term(s)	Aged ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Female ; Humans ; Male ; Nerve Growth Factors/genetics ; Polymorphism, Single Nucleotide ; Risk Assessment ; Sex Factors
Chemical Substances	Nerve Growth Factors
Language	English
Publishing date	2017-05-11
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glx092
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Article ; Online: Family-based tests for associating haplotypes with general phenotype data: Improving the FBAT-haplotype algorithm.

Hecker, Julian / Xu, Xin / Townes, F William / Loehlein Fier, Heide / Corcoran, Chris / Laird, Nan / Lange, Christoph

Genetic epidemiology

2017 Volume 42, Issue 1, Page(s) 123–126

Abstract: For family-based association studies, Horvath et al. proposed an algorithm for the association analysis between haplotypes and arbitrary phenotypes when the phase of the haplotypes is unknown, that is, genotype data is given. Their approach to haplotype ... ...

Abstract	For family-based association studies, Horvath et al. proposed an algorithm for the association analysis between haplotypes and arbitrary phenotypes when the phase of the haplotypes is unknown, that is, genotype data is given. Their approach to haplotype analysis maintains the original features of the TDT/FBAT-approach, that is, complete robustness against genetic confounding and misspecification of the phenotype. The algorithm has been implemented in the FBAT and PBAT software package and has been used in numerous substantive manuscripts. Here, we propose a simplification of the original algorithm that maintains the original approach but reduces the computational burden of the approach substantially and gives valuable insights regarding the conditional distribution. With the modified algorithm, the application to whole-genome sequencing (WGS) studies becomes feasible; for example, in sliding window approaches or spatial-clustering approaches. The reduction of the computational burden that our modification provides is especially dramatic when both parental genotypes are missing. For example, for eight variants and 441 nuclear families with mostly offspring-only families, in a WGS study at the APOE locus, the running time decreased from approximately 21 hr for the original algorithm to 0.11 sec after our modification.
MeSH term(s)	Algorithms ; Apolipoproteins E/genetics ; Cluster Analysis ; Female ; Haplotypes ; Humans ; Male ; Models, Genetic ; Nuclear Family ; Phenotype ; Time Factors ; Whole Genome Sequencing
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2017-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.22094
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Article ; Online: The association of traumatic brain injury with rate of progression of cognitive and functional impairment in a population-based cohort of Alzheimer's disease: the Cache County Dementia Progression Study.

Gilbert, Mac / Snyder, Christine / Corcoran, Chris / Norton, Maria C / Lyketsos, Constantine G / Tschanz, JoAnn T

International psychogeriatrics

2014 Volume 26, Issue 10, Page(s) 1593–1601

Abstract: Background: There is limited research on factors that influence the rate of progression in Alzheimer's disease (AD). A history of traumatic brain injury (TBI) is associated with an increased risk for AD, but its role on the rate of dementia progression ... ...

Abstract	Background: There is limited research on factors that influence the rate of progression in Alzheimer's disease (AD). A history of traumatic brain injury (TBI) is associated with an increased risk for AD, but its role on the rate of dementia progression after the onset of AD has not been examined. Methods: A population-based cohort of 325 persons with incident AD was followed for up to 11 years. The sample was 65% female with a mean (SD) age of dementia onset = 84.4 (6.4) years. History of TBI was categorized as number, severity (with or without loss of consciousness), and timing in relation to dementia onset (within ten years or more than ten years). Cognition was assessed by the Consortium to Establish a Registry of AD battery, and functional ability was assessed by the Clinical Dementia Rating Sum of Boxes. Results: In linear mixed models, a history of TBI within ten years of onset showed faster progression of functional impairment (LR x2 = 10.27, p = 0.006), while those with TBI more than ten years before dementia onset had higher scores on a measure of list learning (β = 1.61, p = 0.003) and semantic memory (β = 0.75, p = 0.0035). Conclusions: History of TBI and its recency may be a useful factor to predict functional progression in the course of AD.
MeSH term(s)	Activities of Daily Living/psychology ; Aged, 80 and over ; Alzheimer Disease/etiology ; Brain Injuries/complications ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Male ; Neuropsychological Tests ; Risk Factors ; Utah/epidemiology
Language	English
Publishing date	2014-05-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1038825-4
ISSN	1741-203X ; 1041-6102
ISSN (online)	1741-203X
ISSN	1041-6102
DOI	10.1017/S1041610214000842
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Article ; Online: Relative risk for Alzheimer disease based on complete family history.

Cannon-Albright, Lisa A / Foster, Norman L / Schliep, Karen / Farnham, James M / Teerlink, Craig C / Kaddas, Heydon / Tschanz, Joann / Corcoran, Chris / Kauwe, John S K

Neurology

2019 Volume 92, Issue 15, Page(s) e1745–e1753

Abstract: Objective: The inherited component for Alzheimer disease (AD) risk has focused on close relatives; consideration of the full family history may improve accuracy and utility of risk estimates.: Methods: A population resource including a genealogy of ... ...

Abstract	Objective: The inherited component for Alzheimer disease (AD) risk has focused on close relatives; consideration of the full family history may improve accuracy and utility of risk estimates. Methods: A population resource including a genealogy of Utah pioneers from the 1800s linked to Utah death certificates was used to estimate relative risk for AD based on specific family history constellations, including from first- to third-degree relatives. Results: Any affected first-degree relatives (FDR) significantly increased risk of AD (≥1 FDRs: relative risk [RR] 1.73, 95% confidence interval [CI] [1.59-1.87]; ≥2 FDRs: RR 3.98 [3.26-4.82]; ≥3 FDRs: RR 2.48 [1.07-4.89]; ≥4 FDRs: RR 14.77 [5.42-32.15]). Affected second-degree relatives (SDR) increased risk even in the presence of affected FDRs (FDR = 1 with SDR = 2: RR 21.29 [5.80-54.52]). AD only in third-degree relatives (TDR) also increased risk (FDR = 0, SDR = 0, TDR ≥3: RR 1.43 [1.21-1.68]). Mixed evidence was observed for differences in risk based on maternal compared to paternal inheritance; higher risks for men than women with equivalent family history, and higher risk for individuals with at least one affected FDR regardless of the relative's age at death, were observed. Conclusions: This population-based estimation of RRs for AD based on family history ascertained from extended genealogy data indicates that inherited genetic factors have a broad influence, extending beyond immediate relatives. Providers should consider the full constellation of family history when counseling patients and families about their risk of AD.
MeSH term(s)	Adult ; Age Factors ; Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Family ; Fathers ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mothers ; Registries ; Risk Assessment ; Sex Factors ; Utah/epidemiology
Language	English
Publishing date	2019-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000007231
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