A Genome-Wide Association Study of Behavioral Disinhibition
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 clust...
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| Vydáno v: | Behavior genetics Ročník 43; číslo 5; s. 363 - 373 |
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| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Boston
Springer US
01.09.2013
Springer Nature B.V |
| Témata: | |
| ISSN: | 0001-8244, 1573-3297, 1573-3297 |
| On-line přístup: | Získat plný text |
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| 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”. |
|---|---|
| AbstractList | 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 x 10 super(-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 super(-5) for one phenotype and p < 10 super(-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". 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^sup -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^sup -5^ for one phenotype and p < 10^sup -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".[PUBLICATION 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".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". 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'. Adapted from the source document. 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 7188 Caucasian individuals clustered in 2300 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 one other phenotype, 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”. 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”. 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". |
| Author | Iacono, William G. Hicks, Brian Miller, Michael B. Oetting, William S. Zhang, Yiwei Basu, Saonli Malone, Steve McGue, Matt Vrieze, Scott |
| AuthorAffiliation | 5 College of Pharmacy, Department of Experimental and Clinical Pharmacology, and the Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA 4 University of Michigan, MI, USA 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA 3 Center for Statistical Genetics, Department of Biostatistics, School of Public Health, University of Michigan, MI, USA 6 Institute of Public Health, University of Southern Denmark, Odense, Denmark 1 Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota, Minneapolis, MN, USA |
| AuthorAffiliation_xml | – name: 5 College of Pharmacy, Department of Experimental and Clinical Pharmacology, and the Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA – name: 3 Center for Statistical Genetics, Department of Biostatistics, School of Public Health, University of Michigan, MI, USA – name: 4 University of Michigan, MI, USA – name: 6 Institute of Public Health, University of Southern Denmark, Odense, Denmark – name: 1 Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota, Minneapolis, MN, USA – name: 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA |
| Author_xml | – sequence: 1 givenname: Matt surname: McGue fullname: McGue, Matt email: mcgue001@umn.edu organization: Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota, Institute of Public Health, University of Southern Denmark – sequence: 2 givenname: Yiwei surname: Zhang fullname: Zhang, Yiwei organization: Division of Biostatistics, School of Public Health, University of Minnesota – sequence: 3 givenname: Michael B. surname: Miller fullname: Miller, Michael B. organization: Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota – sequence: 4 givenname: Saonli surname: Basu fullname: Basu, Saonli organization: Division of Biostatistics, School of Public Health, University of Minnesota – sequence: 5 givenname: Scott surname: Vrieze fullname: Vrieze, Scott organization: Department of Biostatistics, Center for Statistical Genetics, School of Public Health, University of Michigan – sequence: 6 givenname: Brian surname: Hicks fullname: Hicks, Brian organization: Addiction Research Center, University of Michigan – sequence: 7 givenname: Steve surname: Malone fullname: Malone, Steve organization: Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota – sequence: 8 givenname: William S. surname: Oetting fullname: Oetting, William S. organization: Department of Experimental and Clinical Pharmacology, College of Pharmacy, and the Institute of Human Genetics, University of Minnesota – sequence: 9 givenname: William G. surname: Iacono fullname: Iacono, William G. organization: Minnesota Center for Twin and Family Research, Department of Psychology, University of Minnesota |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23942779$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Springer Science+Business Media New York 2013 |
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| DOI | 10.1007/s10519-013-9606-x |
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| Keywords | GCTA Missing heritability GWAS Behavioral disinhibition |
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| Snippet | We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: nicotine, alcohol consumption,... We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: Nicotine, Alcohol Consumption,... |
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| SubjectTerms | Additives Alcohol Alcohol Drinking - genetics Alcohol use Alcoholism Alcoholism - genetics Antisocial personality disorder Associations Behavior Behavioral Science and Psychology Biometrics Candidates Clinical Psychology Comorbidity Disinhibition Drinking behavior Drug abuse Drug use Drugs Families & family life Genetic Predisposition to Disease Genome-Wide Association Study Genomes Genomics Health Psychology Heritability Humans Mental Disorders - genetics Nicotine Original Research Phenotypes Polymorphism, Single Nucleotide Psychology Public Health Smoking Smoking - genetics Substance use disorder Substance-Related Disorders - genetics Twins Variants White people |
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| Title | A Genome-Wide Association Study of Behavioral Disinhibition |
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