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PMID: 17436020 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and maternal generation.

Human genetics ·Vol. 121 ·No. 6 ·2007-07-00 ·Pages 675-84

Devlin B, Klei L, Myles-Worsley M, Tiobech J, Otto C, Byerley W, Roeder K

Abstract

While liability to schizophrenia (Scz) is due to genetic and environmental factors, specific factors are largely unknown. We postulate a two-hit model for Scz, in which initial liability is generated during fetal brain development: this "hit" is precipitated by environmental stressors biologically interacting with maternal genetic vulnerability to the stress. Additional liability to Scz is generated by individual genetic vulnerability. To evaluate these putative levels of vulnerability, we search in the genome of both affected individuals and their mothers for variation that differs, statistically, from that in the general population. For parental analyses, mothers were treated as "affected," rather than their offspring, and the fathers were treated as "controls". We used a sample from the Palauan population: 175 individuals diagnosed with Scz, broadly defined; 87 mothers and 45 fathers of affected individuals. Pedigree and diagnostic data were available on 2,953 living and deceased subjects. DNA from 553 individuals was genotyped for short tandem repeats (STR) spaced approximately every 10 cM across the genome. We tested for association between affection status and STR alleles; such an approach was reasonable, despite the widely spaced markers, because this population has far-ranging linkage disequilibrium (LD). Results for the truly affected individuals were modest, whereas results from the maternal generation were promising. For a recessive model and a test for excess allele matching across mothers, significant findings occurred for D20S481, D10S1221, D6S1021, D13S317, and D18S976. Regions in which at least two adjacent markers produced substantial association statistics include 2p12-11.2, 2q24.1-32.1, 6q12-14.1, 10q23.2-24.21, 12q23.2-24.21 and 17q23.2-23.3.

MeSH Terms
Alleles Blood Group Incompatibility/complications Brain/embryology Diabetes, Gestational/etiology Female Genes, Recessive Genetic Predisposition to Disease Humans Linkage Disequilibrium Male Microsatellite Repeats Models, Biological Models, Genetic Neural Tube Defects/complications Palau Pregnancy Pregnancy Complications/etiology Rh-Hr Blood-Group System Schizophrenia/etiology,genetics
Chemicals
Rh-Hr Blood-Group System
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Devlin Bernie
Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. [email protected]
Klei Lambertus
Myles-Worsley Marina
Tiobech Josepha
Otto Caleb
Byerley William
Roeder Kathryn
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Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
0340-6717
DOI
10.1007/s00439-007-0358-7
Email
[email protected]
Published
2007-07-00
Epub
2007-00-14
Pages
675-84
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
Grants
NIMH NIH HHS · MH063295 · United States
NIMH NIH HHS · R01 MH057881 · United States
NIMH NIH HHS · MH057881 · United States
NIMH NIH HHS · MH063356 · United States
NHGRI NIH HHS · N01-HG-65403 · United States
External Links
PubMed source DOI: 10.1007/s00439-007-0358-7 View journal details
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