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A genome-wide association study of behavioral disinhibition.

ABSTRACT: We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance related behavioral disinhibition. The sample, consisting of 7,188 Caucasian individuals clustered in 2,300 nuclear families, was genotyped on over 520,000 SNP markers from Illumina's Human 660W-Quad Array. Analysis of individual SNP associations revealed only one marker-component phenotype association, between rs1868152 and illicit drugs, with a p value below the standard genome-wide threshold of 5 × 10(-8). Because we had analyzed five separate phenotypes, we do not consider this single association to be significant. However, we report 13 SNPs that were associated at p < 10(-5) for one phenotype and p < 10(-3) for at least two other phenotypes, which are potential candidates for future investigations of variants associated with general behavioral disinhibition. Biometric analysis of the twin and family data yielded estimates of additive heritability for the component phenotypes ranging from 49 to 70%, GCTA estimates of heritability for the same phenotypes ranged from 8 to 37%. Consequently, even though the common variants genotyped on the GWAS array appear in aggregate to account for a sizable proportion of heritable effects in multiple indicators of behavioral disinhibition, our data suggest that most of the additive heritability remains "missing".

SUBMITTER: McGue M

PROVIDER: S-EPMC3886341 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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A genome-wide association study of behavioral disinhibition.

McGue Matt M Zhang Yiwei Y Miller Michael B MB Basu Saonli S Vrieze Scott S Hicks Brian B Malone Steve S Oetting William S WS Iacono William G WG

Behavior genetics 20130814 5

We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance related behavioral disinhibition. The sample, consisting of 7,188 Caucasian individuals clustered in 2,300 nuclear families, was genotyped on over 520,000 SNP markers from Illumina's Human 660W-Quad Array. Analysis of individual SNP associations revealed only one marker-component phenotype as ...[more]

PMID: 23942779

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Project description:BACKGROUND:Bovine respiratory disease complex (BRDC) is one of the most important sources of loss within the beef cattle industry in the USA. Steps have been taken to reduce the incidence of BRDC through vaccination. Despite the effectiveness of vaccines, large proportions of cattle still experience morbidity and mortality. Identification of genomic regions that are associated with variation in response to vaccination would allow for the selection of individuals genetically predisposed to respond to vaccination based on specific markers, while heritability and accuracy estimates would help facilitate genomic selection. This in turn may lead to selection for beef cattle herds that may have lower incidence rate of BRDC after vaccination. This study utilizes an Angus herd of more than 2000 head of cattle to identify these regions of association. RESULTS:Genome wide association studies were performed for viral neutralization antibody level and response to vaccination traits against four different viruses associated with BRDC: bovine viral diarrhea virus 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus (BHV1). A total of six 1-Mb windows were associated with greater than 1% of the genetic variance for the analyzed vaccination response traits. Heritabilities ranged from 0.08 to 0.21 and prediction accuracy ranged from 0.01 to 0.33 across 7 different vaccination traits. CONCLUSIONS:Although six 1-Mb windows were identified as associated with 1% or greater genetic variance for viral neutralization antibody level and response to vaccination traits, few genes around these windows could readily be considered candidates. This indicates the need for further functional genomic annotation, as these regions appear to be gene deserts. Traits ranged from lowly to moderately heritable, which indicated the potential for selection of individuals that are genetically pre-disposed to respond to vaccination. The relatively low amount of genetic variance accounted for by any 1-Mb window indicated that viral neutralization antibody level and response to vaccination traits are polygenic in nature. Selection for these traits is possible, but likely to be slow due to the low heritabilities and absence of markers with high genetic variation associated with them.

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A genome-wide association study of behavioral disinhibition.

Publications

A genome-wide association study of behavioral disinhibition.

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