Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10337228" target="_blank" >RIV/00064203:_____/16:10337228 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10337228

Result on the web

<a href="http://dx.doi.org/10.1002/ajmg.b.32402" target="_blank" >http://dx.doi.org/10.1002/ajmg.b.32402</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ajmg.b.32402" target="_blank" >10.1002/ajmg.b.32402</a>

Result language

angličtina

Original language name

Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Original language description

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R-2=0.0021; P=0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P=0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics

ISSN

1552-4841

e-ISSN

—

Volume of the periodical

171

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

276-289

UT code for WoS article

000371245700015

EID of the result in the Scopus database

2-s2.0-84958168199