Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
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Citations
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References
Research domain criteria (RDoC): toward a new classification framework for research on mental disorders
The Structure of Phenotypic Personality Traits
METAL: fast and efficient meta-analysis of genomewide association scans.
LD score regression distinguishes confounding from polygenicity in genome-wide association studies :
Genomic control for association studies.
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Frequently Asked Questions (14)
Q2. How was the harmonization of personality measures performed in GPC-2?
In GPC-2, harmonization of measures for neuroticism and extraversion across 9 inventories and 29 cohorts was performed by applying Item Response Theory (IRT) to avoid personality scores being influenced by the number of items and the specific inventory.
Q3. What is the meta-analysis of 23andMe and GPC samples?
Given improved power for detection of genetic effects with larger sample sizes in GWAS, the authors performed a combined meta-analysis of 23andMe and GPC samples using METAL54 on the basis of the sample-size based method.
Q4. Why did the authors use only GWAS summary statistics?
Because the authors used only GWAS summary statistics, the authors cannot estimate nonadditive genetic variance, such as dominance and epistasis, or genetic contributions from structural (e.g., inversions) or rare variants.
Q5. What was the phasing of the genotype data of GPC-1?
Genotype data of GPC-1 were then imputed using HapMap phase II CEU (Utah residents with Northern and Western European ancestry from the CEPH collection) as a reference panel including ~2.5 million SNPs6 and, alternatively, a reference panel from 1000 Genomes Project phase 1 version 3 was used to impute the genotype data of GPC-2 (refs. 7,35,36).
Q6. what is the role of chromosome 8p in schizophrenia?
10. Tabarés-Seisdedos, R. & Rubenstein, J.L.R. Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer.
Q7. Why are the personality measures more comparable across GPC-2 cohorts?
Because thepersonality measures were not assessed similarly across GPC-2 cohorts, the harmonized or calibrated scores of personality are more comparable, thereby increasing power for meta-analysis of GWAS using fixed-effect models7,35,36.
Q8. How many SNPs were reduced into 9270,523?
The original 13,341,935 SNPs were reduced into 9,270,523 SNPs in their subsequent analyses (e.g., LD correlation structure is used to determine LD-independent SNPs).
Q9. What is the significance of the correlation between personality traits and psychiatric disorders?
Maladaptive or extreme variants of personality may contribute to the persistence of, or vulnerability to, psychiatric disorders and comorbidity5,11,21,23.
Q10. How many SNPs are in the sample?
156 VOLUME 49 | NUMBER 1 | JANUARY 2017 Nature GeNeticsCaveats of this study include that the sample size, although large, is underpowered to detect the majority of associated SNPs, given the conservative GWAS significance threshold.
Q11. What was the author's consent for the study?
All deCODE studies were approved by the appropriate bioethics and data-protection authorities, and all subjects donating blood provided informed consent.
Q12. What is the phenotypic association between personality traits and mental health?
In addition to phenotypic relationships, twin and GWAS studies have demonstrated genetic correlations between personality traits and psychiatric disorders3,21,23, though most focus on neuroticism (Supplementary Note).
Q13. What were the posterior probabilities for the five hypotheses?
The posterior probabilities (PP0, PP1, PP2, PP3 and PP4) for five hypotheses (H0, no association with either trait; H1, association with trait 1, not with trait 2; H2, association with trait 2, not with trait 1; H3, independent association with two traits, two independent SNPs; H4, association with both traits, one shared SNP)18 were calculated to determine which hypothesis is supported by the data.
Q14. What were the results of the eQTL P analysis?
This procedure resulted in six distributions of eQTL P values that matched the significant SNPs in terms of allele frequencies and TSS, and these were used to determine the ranking of eQTL associations (Supplementary Tables 1 and 5).