Boosting power to detect genetic associations in imaging using multi-locus, genome-wide scans and ridge regression

Omid Kohannim, Derrek P. Hibar, Jason L. Stein, Neda Jahanshad, Clifford R. Jack, Michael W. Weiner, Arthur W. Toga, Paul M. Thompson

Research output: Chapter in Book/Report/Conference proceedingConference contribution

19 Scopus citations

Abstract

Most algorithms used for imaging genetics examine statistical effects of each individual genetic variant, one at a time. We developed a new approach, based on ridge regression, to jointly evaluate multiple, correlated single nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS) of brain images. Our goal was to boost the power to detect gene effects on brain images. We tested our method on MRI-derived hippocampal and temporal lobe volume measures, from 740 subjects scanned by the Alzheimer's Disease Neuroimaging Initiative (ADNI). We identified two significant and one almost significant SNP for the hippocampal and temporal lobe volume phenotypes, respectively, after correcting for multiple statistical tests across the genome. Ridge regression gave more significant associations than univariate analysis. Two SNPs, near regulatory genomic regions, showed significant voxelwise effects in post hoc, tensor-based morphometry analyses. Genome-wide ridge regression may detect SNPs missed by univariate GWAS, by incorporating multi-SNP dependencies in the model.

Original languageEnglish (US)
Title of host publication2011 8th IEEE International Symposium on Biomedical Imaging
Subtitle of host publicationFrom Nano to Macro, ISBI'11
Pages1855-1859
Number of pages5
DOIs
StatePublished - 2011
Event2011 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI'11 - Chicago, IL, United States
Duration: Mar 30 2011Apr 2 2011

Publication series

NameProceedings - International Symposium on Biomedical Imaging
ISSN (Print)1945-7928
ISSN (Electronic)1945-8452

Other

Other2011 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI'11
CountryUnited States
CityChicago, IL
Period3/30/114/2/11

Keywords

  • Alzheimer's Disease
  • GWAS
  • Genome-Wide Association Study
  • Imaging Genetics
  • MRI
  • Neuroimaging
  • Ridge Regression

ASJC Scopus subject areas

  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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