Assessment of the Effect of Age at Onset on Linkage to Bipolar Disorder: Evidence on Chromosomes 18p and 21q  Ping-I Lin, Melvin G. McInnis, James B. Potash, Virginia L. Willour, Dean F. MacKinnon, Kuangyi Miao, J. Raymond DePaulo, Peter P. Zandi  The American Journal of Human Genetics  Volume 77, Issue 4, Pages 545-555 (October 2005) DOI: 10.1086/491602 Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 1 LOD scores along chromosome 21, from the LODPAL analyses of the NIMH sample (n=150 families) and replication sample (n=65 families). Results from the one-covariate model with AAO as a dichotomous variable under the broad- and narrow-phenotype models are shown. For the sake of clarity, baseline models without AAO, which generally yielded LOD scores <0.05, are not shown. The peak finding on chromosome 22q22.13 in the NIMH sample was ∼2.5 Mb away from the peak finding in the replication sample. In both samples, the increased evidence of linkage was observed among affected subjects with early-onset BP (AAO≤21 years). The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 2 Genomewide scan results from the LODPAL analysis under the narrow-phenotype model. The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 3 Genomewide scan results from the LODPAL analysis under the broad-phenotype model. The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 4 Genomewide scan results from the OSA under the narrow-phenotype model. “Baseline” denotes the LOD score in the overall sample. “Low-to-high AAO” denotes the LOD score obtained in the subset ranked by family-specific AAO from low to high values, whereas “High-to-low AAO” denotes the LOD score obtained in the subset ranked by family-specific AAO from high to low values. The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 5 Genomewide scan results from the OSA under the broad-phenotype model. “Baseline” denotes the LOD score in the overall sample. “Low-to-high AAO” denotes the LOD score obtained in the subset ranked by family-specific AAO from low to high values, whereas “High-to-low AAO” denotes the LOD score obtained in the subset ranked by family-specific AAO from high to low values. The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 6 LOD scores along chromosome 18 from the LODPAL and OSA analyses of the NIMH sample (n=150 families) under the broad- and narrow-phenotype models are presented. For the LODPAL analyses, results from the one-covariate model with AAO as a continuous variable are shown. For the OSA analyses, results from the high-to-low slicing of the data set are shown. Baseline models without AAO, which generally yielded LOD scores <0.05, are not shown, for the sake of clarity. The results from both sets of analyses converged at chromosome 18p11.2 and showed increased evidence of linkage among affected subjects with later-onset BP (AAO>21 years). The American Journal of Human Genetics 2005 77, 545-555DOI: (10.1086/491602) Copyright © 2005 The American Society of Human Genetics Terms and Conditions