Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Fatemifar, Ghazaleh; Hoggart, Clive; Paternoster, Lavinia; Kemp, John P.; Prokopenko, Inga; Horikoshi, Momoko; Wright, Victoria J.; Tobias, Jonathan H; Richmond, Stephen; Zhurov, Alexei I.; Toma, Arshed M.; Pouta, Anneli; Taanila, Anja; Sipilä, Kirsi; Lähdesmäki, Raija; Pillas, Demetris; Geller, Frank; Feenstra, Bjarke; Melbye, Mads; Nøhr, Ellen Aagaard; Ring, Susan M.; Pourcain, Beaté St; Timpson, Nicholas J.; Smith, George Davey; Järvelin, Marjo‐Riitta; Evans, David M.

doi:10.1093/hmg/ddt231

Cited by 75 publications

(71 citation statements)

References 60 publications

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“…Samples were genotyped using the Illumina HumanHap550 quad genome-wide SNP genotyping platform as previously described [35]. Individuals were excluded from analyses on the basis of excessive or minimal heterozygosity, gender mismatch, individual missingness (3%), cryptic relatedness as measured by identity by descent (genome-wide IBD 10%) and sample duplication.…”

Section: Methodsmentioning

confidence: 99%

“…Individuals were excluded from analyses on the basis of excessive or minimal heterozygosity, gender mismatch, individual missingness (3%), cryptic relatedness as measured by identity by descent (genome-wide IBD 10%) and sample duplication. Individuals were assessed for population stratification using multi-dimensional scaling modeling seeded with HapMap Phase II release 22 reference populations, and those of non-European ancestry were excluded from further analysis [35]. SNPs with a final call rate of <95%, minor allele frequency <1% and evidence of departure from Hardy–Weinberg equilibrium ( p <5 × 10 −7 ) were also excluded from analyses.…”

Section: Methodsmentioning

confidence: 99%

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Genomic influences on alcohol problems in a population-based sample of young adults

et al. 2015

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Aims Alcohol problems (AP) contribute substantially to the global disease burden. Twin and family studies suggest that AP are genetically influenced, though few studies have identified variants or genes that are robustly associated with risk. This study identifies genetic and genomic influences on AP during young adulthood, which is often when drinking habits are established. Design We conducted a genome-wide association study of AP. We further conducted gene-based tests, gene ontology analyses, and functional genomic enrichment analyses to assess genomic factors beyond single variants that are relevant to AP. Setting The Avon Longitudinal Study of Parents and Children, a large population-based study of a UK birth cohort. Participants Genetic and phenotypic data were available for 4304 participants. Measurements The AP phenotype was a factor score derived from items from the Alcohol Use Disorders Identification Test, symptoms of DSM-IV alcohol dependence, and three additional problem-related items. Findings One variant met genome-wide significance criteria. Four out of 22,880 genes subjected to gene-based analyses survived a stringent significance threshold (q< .05); none of these have been previously implicated in alcohol-related phenotypes. Several biologically plausible gene ontologies were statistically over-represented among implicated SNPs. SNPs on the Illumina 550K SNP chip accounted for ~5% of the phenotypic variance in AP. Conclusions Genetic and genomic factors appear to play a role in alcohol problems in young adults. Genes involved in nervous system-related processes, such as signal transduction and neurogenesis, potentially contribute to liability to alcohol problems, as do genes expressed in non-brain tissues.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Genomic influences on alcohol problems in a population-based sample of young adults

et al. 2015

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“…ALSPAC samples were genotyped using the Illumina HumanHap 550 quad genome-wide SNP genotyping platform, as described previously Fatemifar et al, 2013). Individuals were excluded from analyses on the basis of excessive or minimal heterozygosity, gender mismatch, individual missingness, cryptic relatedness as measured by identity-by-descent (IBD; genome-wide IBD 10%), and sample duplication.…”

Section: Alspac Genotypingmentioning

confidence: 99%

“…Individuals were excluded from analyses on the basis of excessive or minimal heterozygosity, gender mismatch, individual missingness, cryptic relatedness as measured by identity-by-descent (IBD; genome-wide IBD 10%), and sample duplication. Population stratification was assessed using multidimensional scaling modeling seeded with HapMap Phase II release 22 reference populations, and those of non-European ancestry were excluded from further analysis (Fatemifar et al, 2013). Additional quality-control measures included SNPs with a final call rate < 95%, minor allele frequency < 1%, and evidence of departure from Hardy-Weinberg equilibrium (p < 5 × 10 -7 ).…”

Section: Alspac Genotypingmentioning

confidence: 99%

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Savage

Kendler

et al. 2017

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality. Method: We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality. Results: PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence. Conclusions: These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems. (J. Stud. Alcohol Drugs, 78, 442-451, 2017)

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“…Geno-typing and data cleaning protocols have been described extensively elsewhere (Evans et al 2013; Fatemifar et al 2013). Mothers' and children's datasets were cleaned independently yielding 8,365 unrelated individuals in the children's dataset and 8,340 individuals in the mothers' dataset.…”

Section: Application To Real Datamentioning

confidence: 99%

Resolving the Effects of Maternal and Offspring Genotype on Dyadic Outcomes in Genome Wide Complex Trait Analysis (“M-GCTA”)

et al. 2014

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Genome wide complex trait analysis (GCTA) is extended to include environmental effects of the maternal genotype on offspring phenotype (“maternal effects”, M-GCTA). The model includes parameters for the direct effects of the offspring genotype, maternal effects and the covariance between direct and maternal effects. Analysis of simulated data, conducted in OpenMx, confirmed that model parameters could be recovered by full information maximum likelihood (FIML) and evaluated the biases that arise in conventional GCTA when indirect genetic effects are ignored. Estimates derived from FIML in OpenMx showed very close agreement to those obtained by restricted maximum likelihood using the published algorithm for GCTA. The method was also applied to illustrative perinatal phenotypes from ∼4,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children. The relative merits of extended GCTA in contrast to quantitative genetic approaches based on analyzing the phenotypic covariance structure of kinships are considered.

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Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Cited by 75 publications

References 60 publications

Genomic influences on alcohol problems in a population-based sample of young adults

Genomic influences on alcohol problems in a population-based sample of young adults

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Resolving the Effects of Maternal and Offspring Genotype on Dyadic Outcomes in Genome Wide Complex Trait Analysis (“M-GCTA”)

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