Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22

Herbert M. Lachman, John R. Kelsoe, Ronald A. Remick, A. Dessa Sadovnick, Mark H. Rapaport, Margaret Lin, Beverly A. Pazur, Anne Marie A Roe, Takuya Saito, Demitri F. Papolos

Research output: Contribution to journalArticle

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Abstract

Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.

Original languageEnglish (US)
Pages (from-to)121-128
Number of pages8
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume74
Issue number2
DOIs
StatePublished - 1997

Fingerprint

DiGeorge Syndrome
Chromosomes, Human, Pair 22
Bipolar Disorder
British Columbia
Lod Score
Pedigree
Amish
Learning Disorders
Cleft Palate
Microsatellite Repeats
Population
Psychiatry
Schizophrenia
Chromosomes

Keywords

  • bipolar disorder
  • chromosome 22
  • genetic linkage
  • manic depressive illness
  • VCFS
  • velo-cardio-facial syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22. / Lachman, Herbert M.; Kelsoe, John R.; Remick, Ronald A.; Sadovnick, A. Dessa; Rapaport, Mark H.; Lin, Margaret; Pazur, Beverly A.; Roe, Anne Marie A; Saito, Takuya; Papolos, Demitri F.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 74, No. 2, 1997, p. 121-128.

Research output: Contribution to journalArticle

Lachman, Herbert M. ; Kelsoe, John R. ; Remick, Ronald A. ; Sadovnick, A. Dessa ; Rapaport, Mark H. ; Lin, Margaret ; Pazur, Beverly A. ; Roe, Anne Marie A ; Saito, Takuya ; Papolos, Demitri F. / Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 1997 ; Vol. 74, No. 2. pp. 121-128.
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abstract = "Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.",
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T1 - Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22

AU - Lachman, Herbert M.

AU - Kelsoe, John R.

AU - Remick, Ronald A.

AU - Sadovnick, A. Dessa

AU - Rapaport, Mark H.

AU - Lin, Margaret

AU - Pazur, Beverly A.

AU - Roe, Anne Marie A

AU - Saito, Takuya

AU - Papolos, Demitri F.

PY - 1997

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N2 - Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.

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