Abstract
Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 18-23 |
| Number of pages | 6 |
| Journal | Biological Psychiatry |
| Volume | 56 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2004 |
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Keywords
- Epistasis
- GRIK2
- LOD score
- manic-depressive illness
- nonparametric linkage analysis
- prolyl endopeptidase
ASJC Scopus subject areas
- Biological Psychiatry
Cite this
Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. / Schulze, Thomas G.; Buervenich, Silvia; Badner, Judith A.; Steele, C. J M; Detera-Wadleigh, Sevilla D.; Dick, Danielle; Foroud, Tatiana; Cox, Nancy J.; Mackinnon, Dean F; Potash, James Bennett; Berrettini, Wade H.; Byerley, William; Coryell, William; Depaulo, J Raymond; Gershon, Elliot S.; Kelsoe, John R.; McInnis, Melvin G.; Murphy, Dennis L.; Reich, Theodore; Scheftner, William; Nurnberger, John I.; McMahon, Francis J.
In: Biological Psychiatry, Vol. 56, No. 1, 01.07.2004, p. 18-23.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees
AU - Schulze, Thomas G.
AU - Buervenich, Silvia
AU - Badner, Judith A.
AU - Steele, C. J M
AU - Detera-Wadleigh, Sevilla D.
AU - Dick, Danielle
AU - Foroud, Tatiana
AU - Cox, Nancy J.
AU - Mackinnon, Dean F
AU - Potash, James Bennett
AU - Berrettini, Wade H.
AU - Byerley, William
AU - Coryell, William
AU - Depaulo, J Raymond
AU - Gershon, Elliot S.
AU - Kelsoe, John R.
AU - McInnis, Melvin G.
AU - Murphy, Dennis L.
AU - Reich, Theodore
AU - Scheftner, William
AU - Nurnberger, John I.
AU - McMahon, Francis J.
PY - 2004/7/1
Y1 - 2004/7/1
N2 - Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
AB - Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
KW - Epistasis
KW - GRIK2
KW - LOD score
KW - manic-depressive illness
KW - nonparametric linkage analysis
KW - prolyl endopeptidase
UR - http://www.scopus.com/inward/record.url?scp=3042567235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042567235&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2004.04.004
DO - 10.1016/j.biopsych.2004.04.004
M3 - Article
VL - 56
SP - 18
EP - 23
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 1
ER -