|
|
| PMID |
|
|
| TITLE |
|
| A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity. |
|
| ABSTRACT |
|
|
|
| The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2008/03/26 09:00 |
| medline |
2008/11/18 09:00 |
| entrez |
2008/03/26 09:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Holliday EG |
|
Holliday |
E G |
EG |
|
Queensland Centre for Mental Health Research, The Park, Centre for Mental Health, Wacol, Queensland, Australia. lizh@qcmhr.uq.edu.au |
| Mowry BJ |
|
Mowry |
B J |
BJ |
|
|
| Nyholt DR |
|
Nyholt |
D R |
DR |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 147B |
| ISSUE: 7 |
| TITLE: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics |
| ISOABBREVIATION: Am. J. Med. Genet. B Neuropsychiatr. Genet. |
| YEAR: 2008 |
| MONTH: Oct |
| DAY: 5 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1552-485X |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Am J Med Genet B Neuropsychiatr Genet |
| COUNTRY: United States |
| ISSNLINKING: 1552-4841 |
| NLMUNIQUEID: 101235742 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| R01 MH59565 |
NIMH NIH HHS |
United States |
| R01 MH59566 |
NIMH NIH HHS |
United States |
| R01 MH59571 |
NIMH NIH HHS |
United States |
| R01 MH59586 |
NIMH NIH HHS |
United States |
| R01 MH59587 |
NIMH NIH HHS |
United States |
| R01 MH59588 |
NIMH NIH HHS |
United States |
| R01 MH60870 |
NIMH NIH HHS |
United States |
| R01 MH60879 |
NIMH NIH HHS |
United States |
| R01 MH61675 |
NIMH NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| African Americans |
genetics |
| Chromosomes, Human, Pair 5 |
genetics |
| Chromosomes, Human, Pair 7 |
genetics |
| Chromosomes, Human, Pair 8 |
genetics |
| European Continental Ancestry Group |
genetics |
| Genetic Heterogeneity |
genetics |
| Genetic Linkage |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genetics, Population |
genetics |
| Humans |
genetics |
| Lod Score |
genetics |
| Pedigree |
genetics |
| Sample Size |
genetics |
| Schizophrenia |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
