Dataset Information

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

ABSTRACT: Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99?cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10(-8) with nearest gene Enah/Vasp-like (EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86?cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10(-7) with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8?cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43?cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 (RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

SUBMITTER: Merjonen P

PROVIDER: S-EPMC3309462 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Merjonen P P Keltikangas-Järvinen L L Jokela M M Seppälä I I Lyytikäinen L-P LP Pulkki-Råback L L Kivimäki M M Elovainio M M Kettunen J J Ripatti S S Kähönen M M Viikari J J Palotie A A Peltonen L L Raitakari O T OT Lehtimäki T T

Translational psychiatry 20110621

Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phas ...[more]

PMID: 22832427

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Project description:Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ?1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations.From two large Danish cohorts we selected all extremely overweight young men and women (n?=?2,633), and equal numbers of population-based controls (n?=?2,740, drawn randomly from the same populations as the extremes, representing ?212,000 individuals). We followed up novel (at the time of the study) association signals (p<0.001) from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n?=?20,917) and a population-based cohort of 15-year-old British adolescents (n?=?2,418). Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5×10(-8); FTO, MC4R and FAIM2). We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001), and nominal association (p<0.05) at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations.Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all individuals in large population-based studies, which may require tens of thousands of subjects to achieve similar power.

Project description:Lay abstract: It has been proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD), representing the extreme end of this distribution. The current study undertook a genome-wide association (GWA) scan of 965 young Western Australian adults to identify novel risk variants associated with autistic-like traits. No associations reached genome-wide significance; however, a review of nominally associated single nucleotide polymorphisms (SNPs) indicated two positional candidate loci that have been previously implicated in autistic-like trait etiology. Scientific abstract: Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A GWA study using 2,462,046 SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine) Study. No SNP associations reached genome-wide significance (p?<?5.0?×?10(-8)). However, investigations into nominal observed SNP associations (p?<?1.0?×?10(-5)) add support to two positional candidate genes previously implicated in ASD etiology, PRKCB1, and CBLN1. The rs198198 SNP (p?=?9.587?×?10(-6)), is located within an intron of the protein kinase C, beta 1 (PRKCB1) gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p?=?1.78?×?10(-6)) is located in a region flanking the Cerebellin 1 (CBLN1) gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD.

Project description:ObjectiveSedentary behaviour may contribute to the development of obesity. We investigated the relations between different types of sedentary behaviour and adiposity markers in a well-characterised adult population after controlling for a wide range of potential confounders.DesignCross-sectional study.SettingThe Cardiovascular Risk in Young Finns Multicenter Study. Participants Sedentary time (TV viewing, computer time, reading, music/radio listening and other relaxation) was assessed with a questionnaire for 1084 women and 909 men aged 30-45 years. Other study variables included occupational and leisure-time physical activity, sleep duration, socioeconomic status, smoking, alcohol consumption, energy intake, adherence to the recommended diet, multiple individual food items, age and genetic variants associated with body mass index (BMI). Primary outcome measures BMI in kg/m(2) and waist circumference (WC in cm).ResultsOf the different sedentary behaviour types, TV viewing was most consistently related to higher BMI and WC, both in men and women. One additional daily TV hour was associated with a 1.81±0.44 cm larger WC in women and 2 cm±0.44 cm in men (both p<0.0001). The association with TV was diluted, but remained highly significant after adjustments with all measured covariates, including several potentially obesogenic food items associated with TV viewing. The intakes of food items such as sausage, beer and soft drinks were directly associated with TV viewing, while the intakes of oat and barley, fish, and fruits and berries were associated indirectly. After these adjustments, non-TV sedentary behaviour remained associated with adiposity indices only in women.ConclusionsOut of the different types of sedentary behaviour, TV viewing was most consistently associated with adiposity markers in adults. Partial dilution of these associations after adjustments for covariates suggests that the obesogenic effects of TV viewing are partly mediated by other lifestyle factors.

Dataset Information

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Publications

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

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