Olli T Raitakari

Turku University Hospital, Turku, Varsinais-Suomi, Finland

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Publications (639)4278.67 Total impact

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    ABSTRACT: Although physical activity (PA) improves arterial distensibility, it is unclear which type of activity is most beneficial. We aimed to examine the association of different types of PA with carotid distensibility (CD) and the mechanisms involved. Data included 4503 Australians and Finns aged 26-45 years. Physical activity was measured by pedometers and was self-reported. CD was measured using ultrasound. Other measurements included resting heart rate (RHR), cardiorespiratory fitness (CRF), blood pressure, biomarkers and anthropometry. Steps/day were correlated with RHR (Australian men r=-0.10, women r=-0.14; Finnish men r=-0.15, women r=-0.11; P<0.01), CRF and biochemical markers, but not with CD. Self-reported vigorous leisure-time activity was more strongly correlated with RHR (Australian men r=-0.23, women r=-0.19; Finnish men r=-0.20, women r=-0.13; P<0.001) and CRF, and was correlated with CD (Australian men r=0.07; Finnish men r=0.07, women r=0.08; P<0.05). This relationship of vigorous leisure-time activity with CD was mediated by RHR independently of potential confounders. In summary, vigorous leisure-time PA but not total or less intensive PA was associated with arterial distensibility in young to mid-aged adults. Promotion of vigorous PA is therefore recommended among this population. RHR was a key intermediary factor explaining the relationship between vigorous PA and arterial distensibility.Hypertension Research advance online publication, 19 February 2015; doi:10.1038/hr.2015.9.
    Hypertension research : official journal of the Japanese Society of Hypertension. 02/2015;
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    ABSTRACT: High peak bone mass and strong bone phenotype is known to be partly explained by physical activity during growth but there are few prospective studies on this topic. In this 28-year follow-up of Cardiovascular Risk in Young Finns Study cohort, we assessed whether habitual childhood and adolescence physical activity or inactivity at the age of 3-18 years were associated with adult phenotype of weight-bearing tibia and the risk of low-energy fractures. Baseline physical activity and data on clinical, nutritional and lifestyle factors were assessed separately for females and males aged 3-6-years (N=395-421) and 9-18-years (N=923-965). At the age of 31-46-years, the prevalence of low-energy fractures were assessed with a questionnaire and several tibial traits were measured with pQCT (bone mineral content (BMC; mg), total and cortical cross-sectional areas (mm(2)), trabecular (for the distal site only) and cortical (for the shaft only) bone densities (mg/cm(3)), stress-strain index (SSI; mm(3), for the shaft only), bone strength index (BSI; mg(2)/cm(4), for the distal site only) and the cortical strength index (CSI, for the shaft only)). For the statistical analysis, each bone trait was categorized as below the cohort median or the median and above and the adjusted odds ratios (OR) were determined. In females, frequent physical activity at the age of 9-18-years was associated with higher adulthood values of BSI, total and cortical areas, BMC, CSI and SSI at the tibia independently of many health and lifestyle factors (ORs 0.33-0.53, p≤0.05; P-values for trend 0.002-0.05). Cortical density at the tibial shaft showed the opposite trend (P-value for trend 0.03). Similarly in males, frequent physical activity was associated with higher values of adult total and cortical areas and CSI at the tibia (ORs 0.48-0.53, p≤0.05; P-values for trend 0.01-0.02). However, there was no evidence that childhood or adolescence physical activity was associated with lower risk of low energy fractures during the follow-up. In conclusion, frequent habitual physical activity in adolescence seems to confer benefits on tibial bone size and geometry in adulthood. Copyright © 2015. Published by Elsevier Inc.
    Bone 02/2015; · 4.46 Impact Factor
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    ABSTRACT: Context: Low vitamin D levels in adulthood have been associated with cardiovascular disease. Objective: To investigate if low vitamin D levels in childhood are related with increased carotid artery intima-media thickness (IMT) in adulthood. Design, Setting, and Participants: The analyses included 2148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3-18 years at baseline (in 1980). Subjects were re-examined at age 30-45 years (in 2007). Childhood levels of 25-hydroxy-vitamin D were measured from stored serum in 2010. Main Outcome Measure: The carotid artery IMT from 2007 was used. Results: When adjusted for age, sex, and childhood risk factors, continuous data of childhood 25-OH vitamin was inversely associated with adulthood carotid IMT levels among females (β ± SE -0.006 ± 0.003, P = 0.03), but not among males (0.001 ± 0.004, P = 0.88). Children with 25-OH vitamin D levels in the lowest quartile (<40 nmol/L) had significantly increased odds of having high-risk IMT (highest decile of common carotid or carotid bulb IMT or carotid plaque) as adults, in analyses adjusted for age, sex and either childhood risk factors (odds ratio 1.70 [95 % CI 1.15-2.31], P = 0.0007) or adult risk factors, including adult vitamin D levels (odds ratio 1.80 [1.30-2.48], P = 0.0004). In sex-specific analyses, these associations were significant both in females and males (P always <0.05). In sensitivity analyses, those with childhood vitamin D levels in the lowest quintile (<37 nmol/L), gave similar results to those using a quartile cut-point. Conclusions: Low 25-OH vitamin D levels in childhood were associated with increased carotid IMT in adulthood.
    The Journal of clinical endocrinology and metabolism. 02/2015;
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    ABSTRACT: Prediction of adult dyslipidemia has been suggested to improve with multiple measurements in childhood or young adulthood, but there is paucity of specific data from longitudinal studies.
    Atherosclerosis 02/2015; 239(2). · 3.71 Impact Factor
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    ABSTRACT: To examine the association between familial high lipoprotein(a), or Lp(a), concentrations and endothelial function in children participating in the Special Turku Coronary Risk Factor Intervention Project study. Seven-month-old children (n = 1062) with their families were randomized to a risk intervention group or to a control group. The intervention group received individualized dietary counseling to reduce the total cholesterol concentration. Children's Lp(a) and lipid values were measured repeatedly. At age 11 years, children were recruited to an ultrasound study of the flow-mediated dilation (FMD) of the brachial artery. The association between relative peak FMD and Lp(a) concentration was examined in 198 control and 193 intervention group children by linear regression analyses adjusted for sex, total cholesterol concentration, and basal artery diameter. The analyses were made in both the control and intervention groups and in the familial risk children who had a parent with Lp(a) concentration greater than 250 mg/l. Lp(a) concentrations were similar at age 11 years in the intervention and control groups. In all control children, FMD (%) associated inversely with Lp(a) concentration: (β [%/1000 mg/L] = -3.74, 95% CI [-6.43, -1.45]; P = .007) and in 68 familial risk children (β = -4.92, 95% CI [-8.18, -1.66]; P = .0037). In the intervention group the associations were lacking (P > .5), and FMD in the children with high Lp(a) concentrations (>500 mg/L, n = 12) had no attenuation (P = .027). Familial high Lp(a) concentration is associated with attenuated endothelial function. This association may be mitigated by an early lifestyle intervention. ClinicalTrials.gov: NCT00223600. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Pediatrics 02/2015; · 3.74 Impact Factor
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    ABSTRACT: An external or internal “predictive adaptive response” (PAR) can be defined as an adaptive change in long-term behavior or development due to an environmental exposure that triggers it. A PAR can lead to differential development among initially similar individuals, and increase evolutionary fitness. Despite many theories and empirical observations of PAR-like changes in depressive tendencies, clear empirical findings on human personality changes following depressive symptoms are lacking, possibly because these changes take a long time to develop and most follow up studies have been short. Here we show that in sufficiently long (5- and 15-year) clinical and general-population follow ups, increases can be observed in the Temperament and Character Inventory’s personality trait Harm avoidance as a function of temporally accumulating Major Depressive Episodes (132 Depression patients from Vantaa Depression Study) and depressive symptoms (3105 participants from Young Finns general-population sample). Personality changes did not occur in the other six personality traits of the inventory, but did in a highly similar Neuroticism trait from another inventory. Even when controlling for concurrent changes in depressive symptoms from the baseline to the endpoint, depressive symptoms that occurred during the follow-up period associated with Harm-avoidance changes, rendering individuals more fearful and anticipating harm. This study provides consistent, specific, and plausible dose–response and temporal gradients between accumulated depressive episodes and personality change. Effect sizes were between small to moderate, though. Altogether, the findings support the feasibility of using existing systems of personality assessment (i.e., self-report questionnaires) to study PARs, despite the multiplicity of the systems.
    Evolution and Human Behavior 01/2015; · 2.87 Impact Factor
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    ABSTRACT: -Adolescent metabolic syndrome (MetS) predicts type 2 diabetes and subclinical atherosclerosis in adulthood. Our aim was to establish the relation of an infancy-onset dietary intervention on the risk of having MetS between ages 15 and 20 years. -The STRIP study (Special Turku Coronary Risk Factor Intervention Project for Children) is a longitudinal, randomized atherosclerosis prevention trial, where repeated dietary counseling aiming at reducing intake of saturated fat took place from infancy to early adulthood. Participants who had complete data on the MetS components (waist circumference, blood pressure, triglycerides, glucose, HDL-cholesterol) at the age of 15 (n=512), 16 (n=485), 17 (n=475), 18 (n=459), 19 (n=439) and 20 (n=407) years were included in the study. Modified International Diabetes Foundation criteria with 80(th)/20(th) percentile cut-off points for the components was primarily applied in statistical analyses, and the results were replicated using other pediatric MetS definitions. Between ages 15 and 20, the prevalence of Mets varied between 6.0-7.5% in participants in the intervention group and between 10-14% in the control group. The long-term relative risk (RR) of Mets was significantly lower in the intervention group (RR=0.59, 95%CI=0.40-0.88, p=0.009). Of the individual MetS components, the intervention decreased risk of high blood pressure in both sexes (RR=0.83, 95%CI=0.70-0.99) and high triglycerides in males (RR=0.71, 95%CI=0.52-0.98). A statistically non-significant reduction was seen in the risk of high waist circumference in the intervention individuals (RR=0.78, 95%CI=0.59-1.03). -Repeated infancy-onset dietary intervention is effective in the prevention of MetS in adolescence. Clinical Trial Registration Information-ClinicalTrials.gov. Identifier: NCT00223600.
    Circulation 01/2015; · 14.95 Impact Factor
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    ABSTRACT: Objective. To examine factors associated with weight change and obesity risk in young and middle-aged adults. Subjects/methods. The Young Finns Study with its 923 women and 792 men aged 24-39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models. Results. The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain > 2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high childhood BMI, high salt (NaCl and/or KCl) use, low number of children, low childhood family income, high stature and low level of dependence (a temperament subscale) were associated with increased weight gain (in the order of importance). In men (weight gain > 2 kg, n = 455), high stature, high intake of french fries, low intake of sweet cookies, young age, recent divorce, low intake of cereals, high intake of milk, depressive symptoms, rural childhood origin, high baseline BMI and unemployment were associated with more pronounced weight gain. Sedentarity (screen-time) was associated with weight gain only in young men. Physical activity and genetic risk for high BMI (score of 31 known variants) were not consistently associated with weight change. Conclusions. Socio-economic factors, temperamental and physical characteristics, and some dietary factors are related with weight change in young/middle-aged adults. The weight change occurring in adulthood is also determined by childhood factors, such as high BMI and low family income.
    Scandinavian journal of clinical and laboratory investigation. 01/2015;
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    ABSTRACT: There have been calls to know more about vulnerability factors that may predispose to adverse health outcomes at work. We examined if childhood adverse experiences would affect vulnerability to psychosocial stress factors at work. A nationally representative sample of 1546 Finnish men and women was followed up from childhood to adulthood. Childhood adverse experiences consisted of socioeconomic and emotional factors. Job demands and job control were measured 21 years later, and depressive symptoms were measured 21 and 27 years after the childhood measurements. Job demands predicted depressive symptoms over 6 years, and the association was modified by childhood emotional adversity. Participants with three or more emotional adversities in childhood had more depressive symptoms in response to high job demands compared with participants with zero or one emotional adversities in childhood (Betas = −1.40 and −2.01, ps < 0.05 and <0.01). No such moderating effect by childhood adverse experiences was found for the association between job control and depressive symptoms. Although modest in effect size, these findings provide a developmental viewpoint for understanding the role of childhood experiences in work-related stress factors. Such knowledge can enhance understanding of individual differences in vulnerability to the demands of working life. Copyright © 2015 John Wiley & Sons, Ltd.
    Stress and Health 01/2015; · 1.34 Impact Factor
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    ABSTRACT: -The American Heart Association (AHA) has defined a new metric of ideal cardiovascular health as part of its 2020 Impact Goals. We examined whether psychosocial factors in youth predict ideal cardiovascular health in adulthood. -Participants were 477 men and 612 women from the nation-wide Cardiovascular Risk in Young Finns Study. Psychosocial factors were measured from cohorts aged 3 to 18 years at the baseline of the study, and ideal cardiovascular health was examined 27 years later in adulthood. The summary measure of psychosocial factors in youth comprised socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. There was a positive association between a higher number of favorable psychosocial factors in youth and greater ideal cardiovascular health index in adulthood (Beta=0.16, p<0.001) which persisted after adjustment for age, sex, medication use, and cardiovascular risk factors in childhood (Beta=0.15, p<0.001). The association was monotonic, suggesting that each increment in favorable psychosocial factors was associated with improvement in cardiovascular health. Of the specific psychosocial factors, a favorable socioeconomic environment (Beta=0.12, p<0.001) and participants' self-regulatory behavior (Beta=0.07, p=0.004) were the strongest predictors of ideal cardiovascular health in adulthood. -The findings suggest a dose-response association between favorable psychosocial factors in youth and cardiovascular health in adulthood, as defined by the AHA metrics. The effect seems to persist throughout the range of cardiovascular health, potentially shifting the population distribution of cardiovascular health rather than simply having effects in a high-risk population.
    Circulation 01/2015; · 14.95 Impact Factor
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    ABSTRACT: -High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. -We applied quantitative NMR metabolomics to identify biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the SABRE study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes and medication. When further adjusting for routine lipids, four metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation: 1.18 [95%CI 1.12-1.24]; P=4×10(-10)) and monounsaturated fatty acid levels (1.17 [1.11-1.24]; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89 [0.84-0.94]; P=6×10(-5)) and docosahexaenoic acid levels (0.90 [0.86-0.95]; P=5×10(-5)) were associated with lower risk. A risk score incorporating these four biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the two validation cohorts (relative integrated discrimination improvement 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5-10% risk range (net reclassification 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). -Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.
    Circulation 01/2015; · 14.95 Impact Factor
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    ABSTRACT: Objective The present study examined the impact of blood pressure from childhood to mid-adulthood on retinal microvascular architecture.Methods The Cardiovascular Risk in Young Finns Study included children aged 3 to 18 years, from five Finnish University cities, with participants chosen randomly from the national population registrar from those areas. The age of participants included in the current analyses in childhood (1980) ranged from 3 to 9 years and in mid-adulthood (2011) ranged from 34 to 40 years (complete data n=657). Measures of retinal microvasculature architecture measured in adulthood included diameters, tortuosity, lengths and length/diameter ratios.ResultsRegression analysis showed a strong negative association between childhood systolic blood pressure and adult arteriolar diameter (standardized regression coefficient (β) -0.300; p<0.001) and with change in systolic blood pressure from childhood to adulthood (β=-0.249; p<0.001). For arteriolar tortuosity, there was a strong positive association between childhood systolic blood pressure and adult arteriolar tortuosity (β=0.154; p<0.001) and no association with change in systolic blood pressure from childhood to adulthood (β=0.072; p=0.110).Conclusions High blood pressure in childhood and increased blood pressure from childhood to adulthood impacts on retinal microvascular architecture in mid-adulthood.This article is protected by copyright. All rights reserved.
    Microcirculation (New York, N.Y.: 1994) 01/2015; · 2.37 Impact Factor
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    ABSTRACT: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. Trials related to this study were registered at clinicaltrials.gov as NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT01331512 [Invecchiare in Chianti (Aging in the Chianti Area) study], NCT00289237 (Inter99), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis). © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):135-43. · 6.50 Impact Factor
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    ABSTRACT: Background Temperament characteristics have been suggested to be associated with mental health outcomes, especially depression, but the direction of the association is unknown. In this study, we tested whether temperament characteristics, as defined by the Buss–Plomin adulthood emotionality–activity–sociability (EAS) temperament model, predict depressive symptoms or whether depressive symptoms predict changes in temperament characteristics. Methods Participants comprised a population-based sample of 719 men and 1020 women from the Young Finns study aged 20–35 years at baseline in 1997 and who responded to repeated surveys of temperament and depressive symptoms in four study phases from 1997 to 2012. The associations were tested using linear regression models, repeated cross-lagged structural equation models, parallel latent growth curve models and two-dimensional continuous-time state space model (Exact Discrete Model). Results Both low sociability (β=−0.12, p<0.001) and high negative emotionality (β=0.34, p<0.001) predicted subsequent increased depressive symptoms, whereas earlier depressive symptoms predicted increased negative emotionality (β=0.50, p<0.001), but not low sociability. Limitations The depressive symptoms scale applied may not be used for measuring clinically recognized depression. Conclusions Our findings suggest that the direction of the association is from low sociability to depressive symptoms rather than the reverse, but the association between negative emotionality and depressive symptoms seems to be reciprocal.
    Journal of Affective Disorders 01/2015; 170:203–212. · 3.71 Impact Factor
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    ABSTRACT: Fasting insulin concentrations are increasingly being used as a surrogate for insulin resistance and risk for type 2 diabetes (T2DM), although associations with adult outcomes are unclear. Our objective was to determine whether fasting insulin concentrations in childhood associate with later T2DM. Fasting insulin values were available from 2478 participants in the longitudinal Cardiovascular Risk in Young Finns Study at baseline age 3 to 18 years, along with data on adult T2DM (N = 84, mean age = 39.6 years). Among 3- to 6-year-olds, a 1-SD increase in fasting insulin was associated with a relative risk (RR) of 2.04 (95% confidence interval [CI], 1.54-2.70) for later T2DM, which remained significant after we adjusted for BMI and parental history of T2DM. For those aged 9 to 18 years, a 1-SD increase in insulin was associated with an RR of 1.32 (95% CI, 1.06-1.65) for T2DM, but this became nonsignificant after we adjusted for BMI and parental history of T2DM. In the latter age group, a 1-SD increase in BMI was associated with an RR of 1.45 (95% CI, 1.21-1.73) for T2DM, with adjustment for insulin and parental history of T2DM not improving this association. BMI in younger children was not associated with later T2DM. In life course analyses, those with T2DM had higher fasting insulin levels in early childhood and later adulthood but not in peripubertal years. Elevated fasting insulin concentrations in early childhood, but not adolescence, are independently associated with an elevated risk of T2DM in adulthood. Copyright © 2015 by the American Academy of Pediatrics.
    Pediatrics 12/2014; · 5.30 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361.
    Kidney international. 12/2014;
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    ABSTRACT: Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.Molecular Psychiatry advance online publication, 2 December 2014; doi:10.1038/mp.2014.133.
    Molecular Psychiatry 12/2014; · 15.15 Impact Factor
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    ABSTRACT: Elevated serum low-density lipoprotein (LDL) cholesterol is a predictor of cardiovascular disease events, and the quality of dietary fat is known to influence serum concentrations of LDL cholesterol in children. Interindividual differences in response to diet exist, but the underlying genetic factors remain largely unknown. We aimed to identify genetic variants that modify the variation in serum lipid response to dietary fat quality. We used data from 2 longitudinal Finnish cohorts designed to study risk factors for cardiovascular diseases. Large-scale genotyping was performed with Metabochip in a long-term randomized controlled dietary intervention trial, the Special Turku Coronary Risk Factor Intervention Project (STRIP), for discovery of genetic polymorphisms. The observational Cardiovascular Risk in Young Finns Study (YFS) with genome-wide genetic data was used as a replication sample for the initial findings. Dietary records were used to calculate the ratio of unsaturated to saturated fats. Interaction models and multiple follow-ups were used in the analysis. In the STRIP cohort, a variant within the PARK2 locus, rs9364628, showed moderate interaction with dietary fat quality and a consistent direction of effect in both scans on serum LDL-cholesterol concentration in children aged 5 and 7 y (P < 0.0084 and P < 0.0057, respectively). In the YFS cohort, we were unable to replicate the initial discovery signal, but rs12207186 within the PARK2 locus and dietary lipid quality had a stronger interaction effect on serum LDL-cholesterol concentration (P < 9.44 × 10(-5)) than did rs9364628 in children aged 6 y. This genotyping study involving 2 cohorts of healthy Finnish children indicates a possible interaction between PARK2 variants and dietary fat quality on serum LDL-cholesterol concentration. This trial was registered at clinicaltrials.gov as NCT00223600. © 2014 American Society for Nutrition.
    American Journal of Clinical Nutrition 12/2014; 100(6):1569-77. · 6.50 Impact Factor
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    ABSTRACT: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated 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). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; 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-related glycoprotein 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 in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R2 = 0.92). Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
    PLoS Medicine 12/2014; 11(12):e1001765. · 14.00 Impact Factor
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    ABSTRACT: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
    Nature Genetics 12/2014; · 29.65 Impact Factor

Publication Stats

17k Citations
4,278.67 Total Impact Points

Institutions

  • 1998–2015
    • Turku University Hospital
      • • Department of Clinical Physiology and Nuclear Medicine
      • • Turku PET Centre
      Turku, Varsinais-Suomi, Finland
  • 1994–2015
    • University of Turku
      • • Research Centre of Applied and Preventive Cardiovascular Medicine
      • • Department of Clinical Neurophysiology
      • • Turku PET Centre
      Turku, Province of Western Finland, Finland
  • 2013
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
  • 2009–2013
    • University of Tasmania
      • Menzies Research Institute
      Hobart, Tasmania, Australia
    • National Institute for Health and Welfare, Finland
      • Nutrition Unit
      Helsinki, Southern Finland Province, Finland
  • 2008–2013
    • LIKES - Foundation for Sport and Health Sciences
      Jyväskylä, Province of Western Finland, Finland
    • The Royal Children's Hospital
      Melbourne, Victoria, Australia
    • University of Leicester
      • Department of Cardiovascular Sciences
      Leicester, ENG, United Kingdom
  • 2002–2013
    • University of Oulu
      • Institute of Clinical Medicine
      Oulu, Oulu, Finland
  • 1995–2013
    • University of Helsinki
      • • Department of Psychology
      • • Institute for Molecular Medicine Finland (FIMM)
      • • Department of Nutrition
      • • Institute of Behavioural Sciences
      • • Department of Oral Medicine
      Helsinki, Southern Finland Province, Finland
  • 2012
    • Ludwig-Maximilians-University of Munich
      • Department of Internal Medicine I
      München, Bavaria, Germany
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2008–2012
    • Tampere University Hospital (TAUH)
      Tammerfors, Province of Western Finland, Finland
  • 2006–2012
    • Finnish Institute of Occupational Health
      • • Centre of Expertise for Health and Work Ability
      • • Centre of Expertise for Work Organizations
      Helsinki, Province of Southern Finland, Finland
    • Menzies Research Institute
      Hobart Town, Tasmania, Australia
  • 2002–2012
    • University of Tampere
      • • Medical School
      • • Department of Clinical Physiology
      • • Department of Clinical Chemistry
      Tampere, Western Finland, Finland
    • Turku PET Centre
      Turku, Province of Western Finland, Finland
  • 2001–2012
    • University of Jyväskylä
      • Department of Sport Sciences
      Jyväskylä, Province of Western Finland, Finland
  • 2011
    • Tulane University
      • Department of Epidemiology
      New Orleans, LA, United States
    • The University of Warwick
      Coventry, England, United Kingdom
  • 2003–2011
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2010
    • Baker IDI Heart and Diabetes Institute
      Melbourne, Victoria, Australia
  • 2007–2010
    • University College London
      • Department of Epidemiology and Public Health
      London, ENG, United Kingdom
    • University of Texas Health Science Center at San Antonio
      • Department of Pathology
      San Antonio, TX, United States
  • 2008–2009
    • Kuopio University Hospital
      • Department of Obstetrics and Gynaecology
      Kuopio, Province of Eastern Finland, Finland
  • 2006–2009
    • University of Kuopio
      • • Department of Obstetrics and Gynecology
      • • Department of Clinical Nutrition
      Kuopio, Eastern Finland Province, Finland
  • 1999–2009
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia
  • 2005
    • Satakunta Hospital District
      Björneborg, Province of Western Finland, Finland
  • 2004
    • Karolinska Institutet
      • Avdelningen för klinisk fysiologi
      Stockholm, Stockholm, Sweden