Publications
165 results found
Winkler TW, Justice AE, Graff M, et al., 2016, Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study, PLOS Genetics, Vol: 12, Pages: e1006166-e1006166, ISSN: 1553-7390
Okbay A, Beauchamp JP, Fontana MA, et al., 2016, Genome-wide association study identifies 74 loci associated with educational attainment, Nature, Vol: 533, Pages: 539-542, ISSN: 0028-0836
Okbay A, Baselmans BML, De Neve J-E, et al., 2016, Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses, Nature Genetics, Vol: 48, Pages: 624-633, ISSN: 1061-4036
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρˆ| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
Anasanti MD, Kaakinen M, Jarvelin M-R, et al., 2016, Modern Approaches to Address Missing Data in Multi-Phenotype Genome-Wide Association Studies, 45th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 229-229, ISSN: 0001-5652
Kaakinen M, Lagou V, Magie R, et al., 2016, Multi-Phenotype Genome-Wide Meta-Analysis of Lipid Levels and BMI in 64,736 Europeans Suggests Shared Genetic Architecture, 45th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 213-213, ISSN: 0001-5652
Urich A, Kaakinen M, Jiang L, et al., 2016, An Investigation into the Nutrigenomics of Pancreatic Cancer Using Data from the EPIC Study, 45th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 227-228, ISSN: 0001-5652
Linneberg A, Jacobsen RK, Skaaby T, et al., 2015, Effect of smoking on blood pressure and resting heart rate: a Mendelian randomization meta-analysis in the CARTA consortium, Circulation-Cardiovascular Genetics, Vol: 8, Pages: 832-841, ISSN: 1942-325X
Background—Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood.Methods and Results—Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day.Conclusions—This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.
Miettunen J, Nordstrom T, Kaakinen M, et al., 2015, Latent variable mixture modeling in psychiatric research - a review and application, Psychological Medicine, Vol: 46, Pages: 457-467, ISSN: 0033-2917
Latent variable mixture modeling represents a flexible approach to investigating population heterogeneity by sortingcases into latent but non-arbitrary subgroups that are more homogeneous. The purpose of this selective review is to providea non-technical introduction to mixture modeling in a cross-sectional context. Latent class analysis is used to classifyindividuals into homogeneous subgroups (latent classes). Factor mixture modeling represents a newer approach thatrepresents a fusion of latent class analysis and factor analysis. Factor mixture models are adaptable to representing categoricaland dimensional states of affairs. This article provides an overview of latent variable mixture models and illustratesthe application of these methods by applying them to the study of the latent structure of psychotic experiences. Theflexibility of latent variable mixture models makes them adaptable to the study of heterogeneity in complex psychiatricand psychological phenomena. They also allow researchers to address research questions that directly compare the viabilityof dimensional, categorical and hybrid conceptions of constructs.
Kaakinen M, Magi R, Fischer K, et al., 2015, MARV: Anovel method and software tool for genome-wide multi-phenotype analysis of rare variants, Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY-BLACKWELL, Pages: 560-560, ISSN: 0741-0395
Winkler TW, Justice AE, Graff M, et al., 2015, The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study, PLOS GENETICS, Vol: 11, ISSN: 1553-7404
- Author Web Link
- Open Access Link
- Cite
- Citations: 249
Kaakinen M, Maegi R, Fischer K, et al., 2015, Genome-wide multi-phenotype rare variant association analysis detects effect of <i>ZNF259</i> on fasting insulin and triglyceride levels, 51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S143-S143, ISSN: 0012-186X
Morris RW, Taylor AE, Fluharty ME, et al., 2015, Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium, BMJ Open, Vol: 5, ISSN: 2044-6055
Objectives To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.Design Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.Participants 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).Primary outcome measures Waist and hip circumferences, and waist-hip ratio.Results The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by −0.40% (95% CI −0.57% to −0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being −0.31% (95% CI −0.42% to −0.19), −0.08% (−0.19% to 0.03%) and −0.74% (−0.96% to −0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (−0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (−0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.Conclusions For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.
Conlin A, Kyrolainen P, Kaakinen M, et al., 2015, Personality traits and stock market participation, Journal of Empirical Finance, Vol: 33, Pages: 34-50, ISSN: 0927-5398
We analyze the relationship between personality traits and stock market participation. Our sample comes from combining personality trait scores and socioeconomic status information from the Northern Finland Birth Cohort 1966 with data from Finnish Central Securities Depository, the official register of stock holdings in Finland. We find the traits, and especially the subscales of the traits, to be significant predictors of stock market participation. In particular, exploratory excitability, extravagance, sentimentality, and dependence have large effects. One-standard-deviation changes in the subscale scores have marginal effects of up to 4 percentage points on the probability of participating in the stock market.
Warrington NM, Howe LD, Paternoster L, et al., 2015, A genome-wide association study of body mass index across early life and childhood, International Journal of Epidemiology, Vol: 44, Pages: 700-712, ISSN: 0300-5771
Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood.Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were examined in a further 3918 individuals (48 530 measurements) from Northern Finland. Linear mixed effects models with smoothing splines were used in each cohort for longitudinal modelling of BMI.Results: A novel SNP, downstream from the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC and Raine. This association was driven by a difference in BMI at 8 years (T allele of rs944990 increased BMI; PSNP = 1.52 × 10−8), with a modest association with change in BMI over time (PWald(Change) = 0.006). Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10−8) with BMI at 8 years and/or change over time.Conclusions: This GWAS of BMI trajectories over childhood identified a novel locus that warrants further investigation. We also observed genome-wide significance with previously established obesity loci, making the novel observation that these loci affected both the level and the rate of change in BMI. We have demonstrated that the use of repeated measures data can increase power to allow detection of genetic loci with smaller sample sizes.
Cornelis MC, Byrne EM, Esko T, et al., 2015, Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption, MOLECULAR PSYCHIATRY, Vol: 20, Pages: 647-656, ISSN: 1359-4184
- Author Web Link
- Open Access Link
- Cite
- Citations: 178
Fall T, Hagg S, Ploner A, et al., 2015, Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors, DIABETES, Vol: 64, Pages: 1841-1852, ISSN: 0012-1797
- Author Web Link
- Cite
- Citations: 52
Haegg S, Fall T, Ploner A, et al., 2015, Adiposity as a cause of cardiovascular disease: a Mendelian randomization study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 44, Pages: 578-586, ISSN: 0300-5771
- Author Web Link
- Cite
- Citations: 98
Vimaleswaran KS, Berry DJ, Lu C, et al., 2015, Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts, Nutritional Biochemistry: Current Topics in Nutrition Research, Pages: 145-170, ISBN: 9781771881456
Graversen L, Sorensen TIA, Gerds TA, et al., 2015, Prediction of Adolescent and Adult Adiposity Outcomes from Early Life Anthropometrics, OBESITY, Vol: 23, Pages: 162-169, ISSN: 1930-7381
- Author Web Link
- Cite
- Citations: 8
Jiang L, Lagou V, Gutierrez K-S, et al., 2015, Genetic Relationships between Random Glucose, Six Glycaemic Traits and Type 2 Diabetes, 44th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 114-114, ISSN: 0001-5652
Kaakinen M, Claringbould A, Hagenbeek F, et al., 2015, Genome-Wide Multi-Phenotype and eQTL Analyses Provide Novel Insights into Omega Fatty Acid Metabolism, 44th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 115-115, ISSN: 0001-5652
Kaakinen M, Maegi R, Fischer K, et al., 2015, A Novel Method and Software Tool for Genome-Wide Multi-Phenotype Analysis of Rare Variants, 43rd European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 39-39, ISSN: 0001-5652
Wurtz P, Wang Q, Kangas AJ, et al., 2014, Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change, PLOS Medicine, Vol: 11, ISSN: 1549-1277
Background: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to whatextent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemicmetabolite profile in early adulthood.Methods and Findings: We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51%women; mean 6 standard deviation BMI 2464 kg/m2). Circulating metabolites were quantified by high-throughput nuclearmagnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adverselyassociated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses,fatty acid composition, amino acids, inflammatory markers, and various hormones (p,0.0005 for 68 measures). Metaboliteassociations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). Agene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument toassess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%63%;R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p,0.0005 for 24 measures),including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-relatedglycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power.Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change inBMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the crosssectionalobservations, yet with greater metabolic effects (corresp
Taylor AE, Morris RW, Fluharty ME, et al., 2014, Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers, PLOS Genetics, Vol: 10, ISSN: 1553-7390
We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00×10−10), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38×10−5). An interaction test confirmed that these estimates differed from each other (P = 4.95×10−13). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.
Kaakinen M, Sovio U, Hartikainen A-L, et al., 2014, Life course structural equation model of the effects of prenatal and postnatal growth on adult blood pressure, JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, Vol: 68, Pages: 1161-1167, ISSN: 0143-005X
- Author Web Link
- Cite
- Citations: 7
van der Valk RJP, Kreiner-Moller E, Kooijman MN, et al., 2014, A novel common variant in DCST2 is associated with length in early life and height in adulthood, Human Molecular Genetics, Vol: 24, Pages: 1155-1168, ISSN: 1460-2083
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
Taylor AE, Fluharty ME, Bjorngaard JH, et al., 2014, Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium, BMJ Open, Vol: 4, ISSN: 2044-6055
Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach.Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress.Participants: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).Primary outcome measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers.Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the developme
Pillas D, Kaakinen M, Tzoulaki I, et al., 2014, Infant locomotive development and its association with adult blood pressure, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 173, Pages: 1309-1317, ISSN: 0340-6199
- Author Web Link
- Cite
- Citations: 5
de Zeeuw EL, van Beijsterveldt CEM, Glasner TJ, et al., 2014, Polygenic Scores Associated With Educational Attainment in Adults Predict Educational Achievement and ADHD Symptoms in Children, AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, Vol: 165, Pages: 510-520, ISSN: 1552-4841
- Author Web Link
- Cite
- Citations: 33
Cousminer DL, Stergiakouli E, Berry DJ, et al., 2014, Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: 4452-4464, ISSN: 0964-6906
- Author Web Link
- Cite
- Citations: 71
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.