scholarly journals Genetic “General Intelligence,” Objectively Determined and Measured

2019 ◽  
Author(s):  
Javier de la Fuente ◽  
Gail Davies ◽  
Andrew D. Grotzinger ◽  
Elliot M. Tucker-Drob ◽  
Ian J. Deary
Keyword(s):  
Genetic Basis ◽  
Genetic Variance ◽  
Genetic Factors ◽  
General Factor ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Fundamental Dimension ◽  
Cognitive Traits ◽  
Using Data

AbstractIt has been known for 125 years that, in humans, diverse cognitive traits are positively intercorrelated; this forms the basis for the general factor of intelligence (g). We directly test for a genetic basis for g using data from seven different cognitive tests (N = 11,263 to N = 331,679) and genome-wide autosomal single nucleotide polymorphisms. A genetic g factor accounts for 58.4% (SE = 4.8%) of the genetic variance in the cognitive traits, with trait-specific genetic factors accounting for the remaining 41.6%. We distill genetic loci broadly relevant for many cognitive traits (g) from loci associated with only individual cognitive traits. These results elucidate the etiological basis for a long-known yet poorly-understood phenomenon, revealing a fundamental dimension of genetic sharing across diverse cognitive traits.

EpiPen: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

Epi2Loc: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
pp. 272-278 ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, Epi2Loc, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. Epi2Loc facilitates research on SNP–SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

Candidate-gene association study searching for genetic factors involved in migraine chronification

Cephalalgia ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 500-507 ◽  
Author(s):  
MA Louter ◽  
J Fernandez-Morales ◽  
B de Vries ◽  
B Winsvold ◽  
V Anttila ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Factors ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Candidate Gene Association ◽  
Genome Wide ◽  
Third Stage ◽  
Genome Wide Data ◽  
Two Stages

Introduction Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. Methods We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. Results Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. Discussion We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification.

scholarly journals The genetic basis of the human-cannabis relationship

2018 ◽  
Author(s):  
Philippe Henry
Keyword(s):  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Diagnostic Process ◽  
Nucleotide Polymorphisms ◽  
Phenotypic Data ◽  
Single Nucleotide ◽  
Web Based ◽  
Genome Wide ◽  
A Genome ◽  
Shed Light

AbstractCannabis can elicit various reactions in different consumers. In order to shed light on the mechanisms underlying the human-cannabis relationship, we begin to investigate the genetic basis of this differential response. The web-based platform OpenSNP was used to collect selfreported genetic and phenotypic data. Participants either reported a positively or negative affinity to cannabis. A total of 26 individuals were retained, 10 of which indicated several negative responses and the remaining 16 indicating strong affinity for Cannabis. A total of 325’895 single nucleotide polymorphisms (SNPs) were retained. The software TASSEL 5 was used to run a genome-wide association study (GWAS), with a generalized liner model (GLM) and1000 permutations. The analysis yielded a set of 45 SNPs that were significantly associated with the reported affinity to cannabis, including one strong outlier found in the MYO16 gene. A diagnostic process is proposed by which individuals can be assessed for their affinity to cannabis. We believe this type of tool may be helpful in alleviating some of the stigma associated with cannabis use in individuals sensitive to THC and other cannabis constituents such as myrcene, which may potentiate negative responses.

scholarly journals Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data

2019 ◽  
Author(s):  
Mark J. Adams ◽  
David M. Howard ◽  
Michelle Luciano ◽  
Toni-Kim Clarke ◽  
Gail Davies ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Genetic Variance ◽  
Genetic Factors ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Major Depressive ◽  
Genome Wide ◽  
Genetic Contributions

AbstractMajor depressive disorder and neuroticism share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression. We analysed two sets of summary statistics from genome-wide association studies of depression (from the Psychiatric Genomics Consortium and 23andMe) and compared them to GWAS of neuroticism (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only neuroticism, or with both. Second, we estimated partial genetic correlations to test whether the depression’s genetic link with other phenotypes was explained by shared overlap with neuroticism. We found evidence that most genetic variants associated with depression are likely to be shared with neuroticism. The overlapping common genetic variance of depression and neuroticism was negatively genetically correlated with cognitive function and positively genetically correlated with several psychiatric disorders. We found that the genetic contributions unique to depression, and not shared with neuroticism, were correlated with inflammation, cardiovascular disease, and sleep patterns. Our findings demonstrate that, while genetic risk factors for depression are largely shared with neuroticism, there are also non-neuroticism related features of depression that may be useful for further patient or phenotypic stratification.

scholarly journals IL2RA Allele Increases Risk of Neuromyelitis Optica in Southern Han Chinese

2013 ◽  
Vol 40 (6) ◽  
pp. 832-835 ◽  
Author(s):  
Yongqiang Dai ◽  
Jin Li ◽  
Xiaonan Zhong ◽  
Yuge Wang ◽  
Wei Qiu ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Genetic Factors ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Han Chinese ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Interactions ◽  
Genome Wide

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients.Methods:Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing.Results:The rs2104286G frequency in the IL2RA gene was significantly higher in NMO patients than in controls (puncorr=0.013, pcorr=0.026, OR:1.942, 95%CI:1.146-3.291).Conclusion:The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population.

Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5298-5303 ◽  
Author(s):  
David-Alexandre Trégouët ◽  
Simon Heath ◽  
Noémie Saut ◽  
Christine Biron-Andreani ◽  
Jean-François Schved ◽  
...  
Keyword(s):  
Complex Disease ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Fv Leiden ◽  
Gwas Approach

Abstract Venous thromboembolism (VTE) is a complex disease that has a major genetic component of risk. To identify genetic factors that may modify the risk of VTE, we conducted a genome-wide association study by analyzing approximately 317 000 single nucleotide polymorphisms (SNPs) in 453 VTE cases and 1327 controls. Only 3 SNPs located in the FV and ABO blood group genes were found associated with VTE at a genome-wide significant level of 1.7 × 10−7. Detailed analysis of these SNPs in additional cohorts of more than 1700 cases and 1400 controls revealed that the association observed at the FV locus was the result of the increased risk mediated by the FV Leiden mutation, whereas O and A2 blood groups were found to be at lower risk for VTE. Apart from the FV and ABO loci, no other locus was found strongly associated with VTE. However, using this large cohort of subjects, we were able to replicate the mild effects of 2 nonsynonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.

scholarly journals Mining SNPs From EST Databases

1999 ◽  
Vol 9 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Leslie Picoult-Newberg ◽  
Trey E. Ideker ◽  
Mark G. Pohl ◽  
Scott L. Taylor ◽  
Miriam A. Donaldson ◽  
...  
Keyword(s):  
Expressed Sequence Tag ◽  
De Novo ◽  
Cdna Libraries ◽  
Human Populations ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Using Data

There is considerable interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) to enable the analysis of the potential relationships between human genotype and phenotype. Here we present a strategy that permits the rapid discovery of SNPs from publicly available expressed sequence tag (EST) databases. From a set of ESTs derived from 19 different cDNA libraries, we assembled 300,000 distinct sequences and identified 850 mismatches from contiguous EST data sets (candidate SNP sites), without de novo sequencing. Through a polymerase-mediated, single-base, primer extension technique, Genetic Bit Analysis (GBA), we confirmed the presence of a subset of these candidate SNP sites and have estimated the allele frequencies in three human populations with different ethnic origins. Altogether, our approach provides a basis for rapid and efficient regional and genome-wide SNP discovery using data assembled from sequences from different libraries of cDNAs.[The SNPs identified in this study can be found in the National Center of Biotechnology (NCBI) SNP database under submitter handles ORCHID (SNPS-981210-A) and debnick (SNPS-981209-A and SNPS-981209-B).]

scholarly journals Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3

2021 ◽  
Author(s):  
James Nolan ◽  
Purdey J Campbell ◽  
Suzanne J Brown ◽  
Gu Zhu ◽  
Scott Gordon ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Thyroid Function ◽  
Association Analysis ◽  
Genetic Factors ◽  
Meta Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

Objective Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental versus genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Methods Heritability of thyroid stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7,522,526 single nucleotide polymorphisms as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n= 1115) followed by meta-analysis to maximise power for discovery. Results Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Conclusion Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.

scholarly journals STAT4Gene Polymorphisms Are Associated with Susceptibility and ANA Status in Primary Biliary Cirrhosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Satoru Joshita ◽  
Takeji Umemura ◽  
Minoru Nakamura ◽  
Yoshihiko Katsuyama ◽  
Soichiro Shibata ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Genetic Factors ◽  
Association Studies ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Genome Wide ◽  
Mitochondrial Antibody

Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis betweenIL12A,IL12RB, andsignal transducer and activator of transcription 4 (STAT4)genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for severalSTAT4SNPs (rs10168266;P=9.4×10-3, rs11889341;P=1.2×10-3, rs7574865;P=4.0×10-4, rs8179673;P=2.0×10-4, and rs10181656;P=4.2×10-5). Three risk alleles (rs7574865;P=0.040, rs8179673;P=0.032, and rs10181656;P=0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm thatSTAT4is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.

Sign in / Sign up

Export Citation Format

Share Document