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Association of repeatedly measured intermediate risk factors for complex diseases with high dimensional SNP data

Sandra Waaijenborg, Aeilko H Zwinderman
2010 Algorithms for Molecular Biology  
Results: We introduce a method to associate multiple repeatedly measured intermediate risk factors with a high dimensional set of single nucleotide polymorphisms (SNPs).  ...  associated with sets of SNPs.  ...  The Framingham Heart Study research was supported by NHLBI Contract: 2 N01-HC-25195-06 and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278).  ... 
doi:10.1186/1748-7188-5-17 pmid:20205905 pmcid:PMC2828454 fatcat:w6b7wipqnjb2tdmoaamw23vdh4

Associating multiple longitudinal traits with high-dimensional single-nucleotide polymorphism data: application to the Framingham Heart Study

Sandra Waaijenborg, Aeilko H Zwinderman
2009 BMC Proceedings  
We developed a penalized nonlinear canonical correlation analysis to associate multiple repeatedly measured traits with high-dimensional single-nucleotide polymorphism data.  ...  Cardiovascular diseases are associated with combinations of phenotypic traits, which are in turn caused by a combination of environmental and genetic factors.  ...  The full contents of the supplement are available online at http://www.biomedcentral.com/ 1753-6561/3?issue=S7.  ... 
doi:10.1186/1753-6561-3-s7-s47 pmid:20018039 pmcid:PMC2795946 fatcat:7kajl6n7rnbv5khuc5jrbipg4m

Analysis of multiple phenotypes

Jack W. Kent
2009 Genetic Epidemiology  
The complex etiology of common diseases like cardiovascular disease, diabetes, hypertension, and rheumatoid arthritis has led investigators to focus on the genetics of correlated phenotypes and risk factors  ...  All three data sets provided for analysis at the Genetic Analysis Workshop 16 offered multiple quantitative measures of phenotypes related to underlying disease processes as well as discrete measures of  ...  We thank the National Heart, Lung, and Blood Institute; the Framingham Heart Study participants and investigators; and the North American Rheumatoid Arthritis Consortium for providing the data sets.  ... 
doi:10.1002/gepi.20470 pmid:19924720 pmcid:PMC2920037 fatcat:dwo32w5qkvbgjed5ohgch2nzwi

The role of phenotype in gene discovery in the whole genome sequencing era

Laura Almasy
2012 Human Genetics  
Statistical genetic methods and analytical approaches that are concerned with optimizing phenotypes for gene discovery for complex traits offer two general categories of advantages.  ...  Such phenotype optimization approaches include use of allied phenotypes such as symptoms or ages of onset to reduce genetic heterogeneity within a set of cases, study of quantitative risk factors or endophenotypes  ...  Acknowledgments This work was supported in part by R01 MH59490 from the National Institute of Mental Health and R01 GM31575 from the National Institute of General Medical Sciences.  ... 
doi:10.1007/s00439-012-1191-1 pmid:22722752 pmcid:PMC3525519 fatcat:jr4docpnw5ajdiuooipoub6twm

Multivariate Genetic Correlates of the Auditory Paired Stimuli-Based P2 Event-Related Potential in the Psychosis Dimension From the BSNIP Study

Mohammadreza Mokhtari, Balaji Narayanan, Jordan P. Hamm, Pauline Soh, Vince D. Calhoun, Gualberto Ruaño, Mohan Kocherla, Andreas Windemuth, Brett A. Clementz, Carol A. Tamminga, John A. Sweeney, Matcheri S. Keshavan (+1 others)
2015 Schizophrenia Bulletin  
Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component  ...  Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform.  ...  Acknowledgments We thank the study participants for their contributions. J.A.S. has received support from Takeda, BMS, Lilly, Roche and Janssen. M.S.K. has received support from Sunovion.  ... 
doi:10.1093/schbul/sbv147 pmid:26462502 pmcid:PMC4838080 fatcat:oyaxbu72obct7g6gsyo3cf7c6y

Statistical epistasis and progressive brain change in schizophrenia: an approach for examining the relationships between multiple genes

N C Andreasen, M A Wilcox, B-C Ho, E Epping, S Ziebell, E Zeien, B Weiss, T Wassink
2011 Molecular Psychiatry  
In this report we use novel statistical techniques to address the high dimensionality of genomic data, and we apply a refinement in phenotype definition by basing it on the occurrence of brain changes  ...  during the early course of the illness, as measured by repeated MR scans (i.e., an "intermediate phenotype."  ...  Acknowledgments This paper was written with support from the following grants:  ... 
doi:10.1038/mp.2011.108 pmid:21876540 pmcid:PMC3235542 fatcat:rwrlg2iuxjaihfktmqx7pimvri

Phenotypic and genetic markers of psychopathology in a population-based sample of older adults

Arianna M Gard, Erin B Ware, Luke W Hyde, Lauren L Schmitz, Jessica Faul, Colter Mitchell
2021 Translational Psychiatry  
Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry.  ...  Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS).  ...  to complex diseases.  ... 
doi:10.1038/s41398-021-01354-2 pmid:33895785 pmcid:PMC8068727 fatcat:rlhqv3uosjcrnkl74hjfurqvem

Next-generation epidemiology: the role of high-resolution molecular phenotyping in diabetes research

Paul W. Franks, Hugo Pomares-Millan
2020 Diabetologia  
One might view this as next-generation epidemiology, where complex high-dimensionality data analysis approaches will need to be blended with many of the core principles of epidemiological research.  ...  Many are banking on this massive volume of diverse molecular data for breakthroughs in drug discovery and predicting sensitivity to risk factors, response to therapies and susceptibility to diabetes complications  ...  These findings imply that the appropriate use of deep-phenotyping data may enhance the ability to discriminate between high-and low-risk individuals with conventional risk factors and/or disease characteristics  ... 
doi:10.1007/s00125-020-05246-w pmid:32840675 fatcat:uvv37bmgdbbm3ocxcql6r5kz7u

Systems genetics: challenges and developing strategies

Hong Li, Ping Zhang
2012 Biologia (Bratislava)  
Depending on eQTL mapping, one can infer the underlying regulatory network responsible for complex diseases or quantitative trait phenotypes.  ...  Systems genetics research will change the traditional approaches based on reductionism, and allows us to reconsider the living phenomenon and complex disease mechanism.  ...  Measurements of gene expression with high-throughput analysis technologies provide us with an effective approach for learning which types of SNPs in genome are most likely to affect gene regulation, in  ... 
doi:10.2478/s11756-012-0026-9 fatcat:sl3skc3c4fbmtmo7n3pw2klod4

48th European Mathematical Genetics Meeting (EMGM) 2020

Zoltan Kutalik
2020 Human Heredity  
We considered various combinations of factors, including varying effect sizes, variant allele frequencies, numbers of disease SNPs, varying sample sizes and the degree of genetic overlap between the phenotypes  ...  To this end, we performed a simulation study where we repeatedly simulated case-control data sets of varying sizes and with different underlying etiologies from a resampled population of 50,000 individuals  ...  Differentiating between causal and correlated risk factors is of critical importance for disease prevention.  ... 
doi:10.1159/000507248 pmid:32268327 fatcat:3aneluafpnes3a2ayzn53uffca

Machine Learning Prediction of Biomarkers from SNPs and of Disease Risk from Biomarkers in the UK Biobank [article]

Erik Widen, Timothy G. Raben, Louis Lello, Stephen D.H. Hsu
2021 medRxiv   pre-print
For example, our predictor correlates ∼ 0.76 with lipoprotein A level, which is highly heritable and an independent risk factor for heart disease.  ...  We compare polygenic risk scores (risk conditional on genotype: (risk score | SNPs)) for common diseases to the risk predictors which result from the concatenation of learned functions (risk score | biomarkers  ...  The magnitudes of these declines were perhaps expected for correlation chains of generic, high dimensional, vectors with similar pairwise correlations.  ... 
doi:10.1101/2021.04.01.21254711 fatcat:qribo4a3vbhmhavqzgsts72vqy

Systems genetics approaches to understand complex traits

Mete Civelek, Aldons J. Lusis
2013 Nature reviews genetics  
Chen for assistance in the preparation of this paper. M.C. is supported by Ruth L.  ...  of Excellence Award from Foundation Leducq.  ...  factor-binding data, for accurate predictions in complex systems.  ... 
doi:10.1038/nrg3575 pmid:24296534 pmcid:PMC3934510 fatcat:pinns2wz3bh3zjn3pjkxzcrtva

Neurocognitive Phenotypes and Genetic Dissection of Disorders of Brain and Behavior

Eliza Congdon, Russell A. Poldrack, Nelson B. Freimer
2010 Neuron  
Jasinska for assistance with figure preparation and R. Woods, D. Jentsch, R. Bilder for helpful comments on the manuscript.  ...  The e4 allele of APOE, which is the predominant risk variant for common forms of AD, has been repeatedly associated with disease risk, as well as with differences in cognitive abilities in premorbid individuals  ...  to the SNPs that have demonstrated association with complex traits than to other SNPs in the database .  ... 
doi:10.1016/j.neuron.2010.10.007 pmid:20955930 pmcid:PMC4123421 fatcat:ottz4qrfa5b35mijn3ekie6zie

Design and Analysis Issues in Gene and Environment Studies [chapter]

Chen-Yu Liu, Arnab Maity, Xihong Lin, Robert Wright, David Christiani
2013 Epigenetics and Pathology  
We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes.  ...  Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent.  ...  analysis, e.g., for effects of environment of disease phenotypes through epigenetic markers, statistical methods for high-dimensional data analysis for genes and environment, and risk prediction using  ... 
doi:10.1201/b16304-14 fatcat:4jqsocrgsrdcnhmujca2fgj2ea

Design and analysis issues in gene and environment studies

Chen-yu Liu, Arnab Maity, Xihong Lin, Robert O Wright, David C Christiani
2012 Environmental Health  
We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes.  ...  Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent.  ...  analysis, e.g., for effects of environment of disease phenotypes through epigenetic markers, statistical methods for high-dimensional data analysis for genes and environment, and risk prediction using  ... 
doi:10.1186/1476-069x-11-93 pmid:23253229 pmcid:PMC3551668 fatcat:kajcfwvo5vhfvjssl4luaa7fey
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