How to Cite this Article: Howrigan DP, Laird NM, Smoller JW, Devlin B, McQueen MB. 2011. Using Linkage Information to Weight a Genome-Wide Association of Bipolar Disorder. Am J Med Genet Part B 156:462–471.
Using linkage information to weight a genome-wide association of bipolar disorder†
Article first published online: 7 APR 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 4, pages 462–471, June 2011
How to Cite
Howrigan, D.P., Laird, N.M., Smoller, J.W., Devlin, B. and McQueen, M.B. (2011), Using linkage information to weight a genome-wide association of bipolar disorder. Am. J. Med. Genet., 156: 462–471. doi: 10.1002/ajmg.b.31183
- Issue published online: 25 APR 2011
- Article first published online: 7 APR 2011
- Manuscript Accepted: 2 MAR 2011
- Manuscript Received: 25 NOV 2010
- National Institute of Child Health and Human Development. Grant Number: T32 HD007289
- National Institute of Mental Health. Grant Number: T32 MH016880
- National Institute on Drug Abuse. Grant Number: DA011015
- National Institute of Mental Health. Grant Number: MH063445
- biploar disorder;
- genome-wide association;
- weighted false discovery approach
Issues of multiple-testing and statistical significance in genome-wide association studies (GWAS) have prompted statistical methods utilizing prior data to increase the power of association results. Using prior findings from genome-wide linkage studies on bipolar disorder (BPD), we employed a weighted false discovery approach (wFDR; [Roeder et al. 2006. Am J Hum Genet 78(2): 243–252]) to previously reported GWAS data drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Using this method, association signals are up or down-weighted given the linkage score in that genomic region. Although no SNPs in our sample reached genome-wide significance through the wFDR approach, the strongest single SNP result from the original GWAS results (rs4939921 in myosin VB) is strongly up-weighted as it occurs on a linkage peak of chromosome 18. We also identify regions on chromosome 9, 17, and 18 where modestly associated SNP clusters coincide with strong linkage scores, implicating them as possible candidate regions for further analysis. Moving forward, we believe the application of prior linkage information will be increasingly useful to future GWAS studies that incorporate rarer variants into their analysis. © 2011 Wiley-Liss, Inc.