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Study Report
Comment on Study | View All Comments on Study |
Reference | Greenwood, T. A.,2012 PMID: 22329474 |
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Citation | Greenwood, T. A., C. M. Nievergelt, et al. (2012). "Further evidence for linkage of bipolar disorder to chromosomes 6 and 17 in a new independent pedigree series." Bipolar Disord 14(1): 71-79. |
Disease Type | Bipolar Disorder |
Study Design | pedigree |
Study Type | Genome-wide Linkage Study |
Sample Size | 229 individuals from 34 families |
SNP/Region/Marker Size | whole genome wide with 440 markers |
Predominant Ethnicity | |
Population | American and Canadian |
Sample Diagnosis | DSM |
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Sample Status | Families were ascertained from the general North American population through both a systematic survey of clinical facilities, and through advertising and patient support groups from three sites: (i) San Diego, CA, USA; (ii) Vancouver, BC, Canada; and(iii) Cincinnati, OH, USA. Families were ascertained through a proband with bipolar disorder I or II and included if at least two additional members had either BD or recurrent major depressive disorder(MDD). We purposely chose broad criteria for ascertainment to better reflect families with BD in the population. Following informed consent procedures approved by the local institutional review boards (IRB) of the collaborative sites, the proband and all participating family members were interviewed directly using the Structured Clinical Interview for DSM-III-R (SCID) (12). Bipolar II disorder was diagnosed as BD not otherwise specified, modified so as to require a minimum duration of two days for hypomania. |
Technique | Genotyping |
Statistical Method | All analyses were performed under two diagnostic models of affection: (i) a narrow model (BD) that included diagnoses of bipolar I disorder, bipolar II disorder, and schizoaffective disorder (bipolar type); and (ii) a broad model (BD+MDD)that included a diagnosis from the narrow model plus a diagnosis of recurrent MDD.Initial analyses were performed using model-free, nonparametric two-point, and multipoint linkage analyses methods in Merlin to analyze the extent of allele sharing among all affected relative pairs (16). Marker allele frequencies were estimated among all individuals, the default in Merlin. Logarithm of odds (LOD) scores and corresponding p-values were converted from nonparametric scores using the Kong-and-Cox function (19) and were computed for each marker for two-point analyses. For the multipoint analyses,LOD scores and p-values were computed at a 1-cM interval across the chromosome, beginning with the first marker. |
Result Summary | Initial nonparametric analyses of chromosomes 6 and 17 provided evidence for a modest replication of linkage to these chromosomes previously reported in other studies. Additional analyses using multipoint parametric methods provided further evidence to support the 6q25 region with a heterogeneity logarithm of odds score of 3.28. Evidence from two-point parametric analyses also provides a modest replication of our previous findings of linkage to the 23 cM region of chromosome 22q13 in our original University of California, San Diego sample of 20 families and 57 families from the National Institute of Mental Health bipolar disorder sample. CONCLUSIONS: Our results suggest replication of some reported linkage peaks, such as 6q25 and 17p12; however, other peaks from our own previous study, such as 5p15, 13q32, and 22q13, were either not replicated or were only modestly replicated in these analyses. |
Region | Statistical Values | Author Comments | Result Category |
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8q24 | Linkage analysis: for BD+MDD, LOD = 1.17 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
9q31 | Linkage analysis: for BD, LOD = 1.91 | Suggestive linkage was found in this region. Suggestive linkage was found in this region. | Trend |
Xq25 | Linkage analysis: for BD+MDD, LOD = 1.45, MLOD = 1.21 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
6q16 | Linkage analysis: for BD, MLOD = 1.61 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
4p16 | Linkage analysis: for BD+MDD, MLOD = 1.46 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
7q21 | Linkage analysis: for BD, LOD = 1.27 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
6q25 | Linkage analysis: for BD+MDD, LOD = 1.03, MLOD = 1.51, HOLD = 3.28 | Suggestive linkage was found in this region. Suggestive linkage was found in this region. | Trend |
20q11 | Linkage analysis: for BD, LOD = 1.27, MLOD = 2.01 | Suggestive linkage was found in this region. Suggestive linkage was found in this region. | Trend |
1q23 | Linkage analysis: for BD, LOD = 1.67 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
2q35 | Linkage analysis: for BD, MLOD = 1.35 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
22q11 | Linkage analysis: for BD, LOD = 1.21, for BD+MDD, LOD = 1.4 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
17p12 | Linkage analysis: for BD, LOD = 1.27, MLOD = 2.12 | Suggestive linkage was found in this region. Suggestive linkage was found in this region. | Trend |
16q22 | Linkage analysis: for BD, LOD = 1.13 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
17q21 | Linkage analysis: for BD, MLOD = 1.39 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
17p13 | Linkage analysis: for BD, LOD = 1.64 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
13q32 | Linkage analysis: for BD+MDD, LOD = 1.28 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
15q21 | Linkage analysis: for BD, MLOD = 1.85, for BD+MDD, MLOD = 1.78 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
14q22 | Linkage analysis: for BD, MLOD = 1.22 | No significant linkage was found in this region. No significant linkage was found in this region. | Negative |
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
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Last update: March 31, 2016