Dominic Holland
University of California, San Diego
Genome-wide association studyInternal medicineSample size determinationPathologyMagnetic resonance imagingSingle-nucleotide polymorphismPsychologyNeuroscienceGenetic associationAlzheimer's Disease Neuroimaging InitiativeDiseaseDementiaAtrophyLinkage disequilibriumAlzheimer's diseaseNeuroimagingComputational biologyMedicineBiologyGenetic architecture
135Publications
49H-index
7,380Citations
Publications 106
Newest
#1Dominic Holland (UCSD: University of California, San Diego)H-Index: 49
#2Oleksandr Frei (University of Oslo)H-Index: 19
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 8 authors...
We propose an extended Gaussian mixture model for the distribution of causal effects of common single nucleotide polymorphisms (SNPs) for human complex phenotypes that depends on linkage disequilibrium (LD) and heterozygosity (H), while also allowing for independent components for small and large effects. Using a precise methodology showing how genome-wide association studies (GWASs) summary statistics (z-scores) arise through LD with underlying causal SNPs, we applied the model to GWAS of multi...
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#1Xiangyu Yang (The Ohio State University Wexner Medical Center)
#1Ana E. Rodríguez-Soto (UCSD: University of California, San Diego)H-Index: 7
Last. Rebecca Rakow-Penner (UCSD: University of California, San Diego)H-Index: 13
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BACKGROUND Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to B0 inhomogeneities. Both prospective and retrospective approaches have been developed to decrease and correct such distortions. PURPOSE The purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance...
1 CitationsSource
#1Christopher C. Conlin (UCSD: University of California, San Diego)H-Index: 3
#2Christine H. Feng (UCSD: University of California, San Diego)H-Index: 5
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 10 authors...
BACKGROUND Multicompartmental modeling outperforms conventional diffusion-weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer. PURPOSE To optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo. STUDY TYPE Retrospective. SUBJECTS Forty-six patients who underwent MRI examination for suspected prostate cancer; 2...
1 CitationsSource
#1Alexey A. Shadrin (University of Oslo)H-Index: 12
#2Tobias Kaufmann (University of Oslo)H-Index: 35
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 21 authors...
Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we exploit the distributed nature of genetic effects across the brain and apply the Multivariate Omnibus Statistical Test (MOSTest) to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) measures from N=35,657 participants in the UK Biobank. We identified 1598 loci for cortical surface area ...
3 CitationsSource
#1Alexey A. Shadrin (University of Oslo)H-Index: 12
#2Oleksandr Frei (University of Oslo)H-Index: 19
Last. Anders M. DaleH-Index: 166
view all 12 authors...
MOTIVATION Determining the relative contributions of functional genetic categories is fundamental to understanding the genetic etiology of complex human traits and diseases. Here we present Annotation Informed (AI)-MiXeR, a likelihood-based method for estimating the number of variants influencing a phenotype and their effect sizes across different functional annotation categories of the genome using summary statistics from genome-wide association studies. RESULTS Extensive simulations demonstrat...
2 CitationsSource
#1Dennis van der Meer (UM: Maastricht University)H-Index: 20
#2Oleksandr Frei (University of Oslo)H-Index: 19
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 12 authors...
1 CitationsSource
#1Dennis van der Meer (UM: Maastricht University)H-Index: 20
#2Oleksandr Frei (University of Oslo)H-Index: 19
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 12 authors...
Regional brain morphology has a complex genetic architecture, consisting of many common polymorphisms with small individual effects. This has proven challenging for genome-wide association studies (GWAS). Due to the distributed nature of genetic signal across brain regions, multivariate analysis of regional measures may enhance discovery of genetic variants. Current multivariate approaches to GWAS are ill-suited for complex, large-scale data of this kind. Here, we introduce the Multivariate Omni...
9 CitationsSource
#1Eero Vuoksimaa (UH: University of Helsinki)H-Index: 26
#2Linda K. McEvoy (UCSD: University of California, San Diego)H-Index: 66
view all 5 authors...
Mild cognitive impairment (MCI) is a heterogeneous condition with variable outcomes. Improving diagnosis to increase the likelihood that MCI reliably reflects prodromal Alzheimer’s Disease (AD) would be of great benefit for clinical practice and intervention trials. In 230 cognitively normal (CN) and 394 MCI individuals from the Alzheimer’s Disease Neuroimaging Initiative, we studied whether an MCI diagnostic requirement of impairment on at least two episodic memory tests improves 3-year predict...
7 CitationsSource
#1Christopher C. Conlin (UCSD: University of California, San Diego)H-Index: 3
#2Christine H. Feng (UCSD: University of California, San Diego)H-Index: 5
Last. Anders M. Dale (UCSD: University of California, San Diego)H-Index: 166
view all 10 authors...
Background Optimizing a restriction spectrum imaging (RSI) model for the prostate could lead to improved characterization of diffusion in the prostate and better discrimination of tumors. Purpose To determine optimal apparent diffusion coefficients (ADCs) for prostate RSI models and evaluate the number of tissue compartments required to best describe diffusion in prostate tissue. Study Type Retrospective. Population/Subjects Thirty-six patients who underwent an extended MRI examination for suspe...
1 CitationsSource
#1Olav B. Smeland (Oslo University Hospital)H-Index: 22
#2Oleksandr Frei (Oslo University Hospital)H-Index: 19
Last. Ole A. Andreassen (Oslo University Hospital)H-Index: 123
view all 11 authors...
In recent years, genome-wide association study (GWAS) sample sizes have become larger, the statistical power has improved and thousands of trait-associated variants have been uncovered, offering new insights into the genetic etiology of complex human traits and disorders. However, a large fraction of the polygenic architecture underlying most complex phenotypes still remains undetected. We here review the conditional false discovery rate (condFDR) method, a model-free strategy for analysis of GW...
22 CitationsSource