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2. Childhood dyslipidemia and carotid atherosclerotic plaque in adulthood:the Cardiovascular Risk in Young Finns Study

Author

Koskinen, J. S. (Juhani S.), Kytö, V. (Ville), Juonala, M. (Markus), Viikari, J. S. (Jorma S. A.), Nevalainen, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Hutri-Kähönen, N. (Nina), Laitinen, T. P. (Tomi P.), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Magnussen, C. G. (Costan G.), Raitakari, O. T. (Olli T.), Koskinen, J. S. (Juhani S.), Kytö, V. (Ville), Juonala, M. (Markus), Viikari, J. S. (Jorma S. A.), Nevalainen, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Hutri-Kähönen, N. (Nina), Laitinen, T. P. (Tomi P.), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Magnussen, C. G. (Costan G.), and Raitakari, O. T. (Olli T.)

Abstract

Background: Childhood exposure to dyslipidemia is associated with adult atherosclerosis, but it is unclear whether the long‐term risk associated with dyslipidemia is attenuated on its resolution by adulthood. We aimed to address this question by examining the links between childhood and adult dyslipidemia on carotid atherosclerotic plaques in adulthood. Methods and Results: The Cardiovascular Risk in Young Finns Study is a prospective follow‐up of children that began in 1980. Since then, follow‐up studies have been conducted regularly. In 2001 and 2007, carotid ultrasounds were performed on 2643 participants at the mean age of 36 years to identify carotid plaques and plaque areas. For childhood lipids, we exploited several risk factor measurements to determine the individual cumulative burden for each lipid during childhood. Participants were categorized into the following 4 groups based on their childhood and adult dyslipidemia status: no dyslipidemia (reference), incident, resolved, and persistent. Among individuals with carotid plaque, linear regression models were used to study the association of serum lipids with plaque area. The prevalence of plaque was 3.3% (N=88). In models adjusted for age, sex, and nonlipid cardiovascular risk factors, the relative risk for carotid plaque was 2.34 (95% CI, 0.91–6.00) for incident adult dyslipidemia, 3.00 (95% CI, 1.42–6.34) for dyslipidemia resolved by adulthood, and 5.23 (95% CI, 2.57–10.66) for persistent dyslipidemia. Carotid plaque area correlated with childhood total, low‐density lipoprotein, and non–high‐density lipoprotein cholesterol levels. Conclusions: Childhood dyslipidemia, even if resolved by adulthood, is a risk factor for adult carotid plaque. Furthermore, among individuals with carotid plaque, childhood lipids associate with plaque size. These findings highlight the importance of primordial prevention of dyslipidemia in childhood to reduce atherosclerosis development.

Published
2023

3. The relationship between temperament, polygenic score for intelligence and cognition:a population-based study of middle-aged adults

Author

Tölli, P. (Pekka), Keltikangas-Järvinen, L. (Liisa), Lehtimäki, T. (Terho), Ravaja, N. (Niklas), Hintsanen, M. (Mirka), Ahola-Olli, A. (Ari), Pahkala, K. (Katja), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Laitinen, T. T. (Tomi T.), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Dobewall, H. (Henrik), Jokinen, E. (Eero), Raitakari, O. (Olli), Cloninger, C. R. (C. Robert), Rovio, S. (Suvi), Saarinen, A. (Aino), Tölli, P. (Pekka), Keltikangas-Järvinen, L. (Liisa), Lehtimäki, T. (Terho), Ravaja, N. (Niklas), Hintsanen, M. (Mirka), Ahola-Olli, A. (Ari), Pahkala, K. (Katja), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Laitinen, T. T. (Tomi T.), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Dobewall, H. (Henrik), Jokinen, E. (Eero), Raitakari, O. (Olli), Cloninger, C. R. (C. Robert), Rovio, S. (Suvi), and Saarinen, A. (Aino)

Abstract

We investigated whether temperament modifies an association between polygenic intelligence potential and cognitive test performance in midlife. The participants (n = 1647, born between 1962 and 1977) were derived from the Young Finns Study. Temperament was assessed with Temperament and Character Inventory over a 15-year follow-up (1997, 2001, 2007, 2012). Polygenic intelligence potential was assessed with a polygenic score for intelligence. Cognitive performance (visual memory, reaction time, sustained attention, spatial working memory) was assessed with CANTAB in midlife. The PGSI was significantly associated with the overall cognitive performance and performance in visual memory, sustained attention and working memory tests but not reaction time test. Temperament did not correlate with polygenic score for intelligence and did not modify an association between the polygenic score and cognitive performance, either. High persistence was associated with higher visual memory (B = 0.092; FDR-adj. p = 0.007) and low harm avoidance with higher overall cognitive performance, specifically better reaction time (B = −0.102; FDR-adj; p = 0.007). The subscales of harm avoidance had different associations with cognitive performance: higher “anticipatory worry,” higher “fatigability,” and lower “shyness with strangers” were associated with lower cognitive performance, while the role of “fear of uncertainty” was subtest-related. In conclusion, temperament does not help or hinder one from realizing their genetic potential for intelligence. The overall modest relationships between temperament and cognitive performance advise caution if utilizing temperament-related information e.g. in working-life recruitments. Cognitive abilities may be influenced by temperament variables, such as the drive for achievement and anxiety about test performance, but they involve distinct systems of learning and memory.

Published
2022

6. Puurakentamisen terveysvaikutukset – Tutkimuksella tietoperusteista tukea puurakentamiselle ja puun käyttömuotojen lisäämiselle:loppuraportti

Author

Jokinen, E. (Elina), Sutinen, V. (Veijo), Kilpeläinen, P. (Pekka), and Virtanen, V. (Vesa)

Subjects
stress, wellbeing, haihtuvat orgaaniset yhdisteet, volatile organic compounds, sisäilma, hyvinvointi, wood construction, IoT-teknologia, indoor air, stressi, puurakentaminen, IoT technology
Abstract

Wooden buildings have a good reputation. They are considered pleasant in appearance, not to have problems with indoor air and even promote well-being. Short-stay tests carried out in controlled conditions support these assumptions. On the other hand, studies on how long-term living or working in a wooden building affects people, as far as we know, are nearly lacking besides resident satisfaction surveys. The only exception is a follow-up study of two groups of schoolchildren with under 20 people, carried out in Austria at the beginning of 2010’s. In this study, Tuupala wooden school in Kuhmo and as a reference Tuupala stone school and a primary school in town of Vaala were monitored for temperature, indoor air humidity, carbon dioxide content, particulate matter and total concentration of volatile organic compounds by IoT sensors for 10 months. Samples of indoor air were taken to determine individual volatile organic compounds and microbiological quality. Noise level in the classrooms was monitored for one month. In three weeks during the study, concentration of the stress hormone cortisol was monitored in daily saliva samples. A total of approximately 1,300 saliva samples from schoolchildren were collected in the primary schools in both Kuhmo and Vaala. In addition, smaller groups of schoolchildren were monitored for the stress with a smart ring that measured electrodermal activity. Based on the results, the wooden school of Tuupala is an excellent learning environment for its schoolchildren. It has a quiet and peaceful noise level. The variation in humidity is lower there than in the control school, and stress of schoolchildren is lower than in the classes of the control school. The difference in the stress is in some time periods statistically significant. Of course, the results of the study do not show that all wooden schools are equally good or that similar results cannot be achieved in other types of schools as well. The wooden building does likely not explain all the results, but it is certainly one important factor in a good school environment. This study was funded by the Finnish Forest Foundation and the European Agricultural Funds for Rural Development of Mainland Finland. The study was carried out during 2020 by the Unit of Measurement Technology of the University of Oulu at the Kajaani University Centre. Tiivistelmä Puurakennuksilla on hyvä maine. Niitä pidetään ulkonäöltään miellyttävinä ja sisäilmaltaan ongelmattomina ja jopa hyvinvointia edistävinä. Kontrolloiduissa olosuhteissa tehdyt lyhytaikaista oleskelua seuranneet kokeet myös tukevat näitä oletuksia. Sen sijaan tutkimuksia siitä kuinka pitkäaikainen asuminen tai työskentely puurakennuksessa vaikuttaa henkilöihin on tietääksemme selvitetty vain asukastyytyväisyyskyselyillä sekä yhdessä Itävallassa 2010-luvun alussa tehdyssä kahden vajaan 20 hengen koululaisryhmän seurannassa. Puurakentamisen terveysvaikutukset -tutkimuksessa seurattiin Kuhmon Tuupalan puukoulun sekä verrokkina olleiden Tuupalan kivikoulun ja Vaalan yhtenäiskoulun lämpötilaa, sisäilman kosteutta, hiilidioksidin pitoisuutta, paine-eroa, pienpartikkeleiden määrää ja haihtuvien orgaanisten yhdisteiden kokonaismäärää jatkuvatoimisella sensoriseurannalla 10 kuukauden ajan. Sisäilmasta otettiin näytteitä haihtuvien orgaanisten yhdisteiden ja mikrobiologisen laadun yksityiskohtaiseksi selvittämiseksi. Äänenvoimakkuutta ja valoisuutta luokkahuoneissa seurattiin yhden kuukauden ajan. Kolmena tutkimusviikkona seurattiin päivittäin otetuista sylkinäytteistä stressihormoni kortisolin pitoisuutta. Sylkinäytteitä kerättiin sekä Kuhmossa että Vaalassa alakoulun kolmen luokan oppilailta yhteensä noin 1300. Lisäksi pienemmissä ryhmissä seurattiin koululaisten stressaantuneisuutta ihon sähköistä aktiivisuutta mitanneella älysormuksella. Tutkimuksen perusteella Tuupalan puukoulu on erinomainen opiskeluympäristö koululaisilleen. Se on melutasoltaan hiljainen ja rauhallinen. Ilmankosteuden vaihtelu on siellä tutkimuksen verrokkikoulua vähäisempää ja koululaisten stressaantuneisuus on vähäisempää kuin verrokkikoulun luokissa. Ero stressaantuneisuudessa on ajoittain tilastollisesti merkittävää. Tutkimustulokset eivät tietenkään osoita, että kaikki puukoulut olisivat yhtä hyviä tai etteikö samanlaisia tuloksia voitaisi saavuttaa myös muunlaisissa kouluissa. Puinen rakennus tuskin on ainoa selittävä tekijä kaikille tuloksille, mutta se varmasti on yksi tärkeä tekijä hyvässä kouluympäristössä. Tutkimuksen rahoittajat olivat Suomen Metsäsäätiö ja Manner-Suomen maaseuturahasto. Tutkimuksen toteuttaja oli Oulun yliopiston Mittaustekniikan yksikkö Kajaanin yliopistokeskuksesta. Tutkimus toteutettiin vuoden 2020 aikana.

Published
2021

8. Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)

Author

Cuthbertson, DJ, Koskinen, J, Brown, E, Magnussen, CG, Hutri-Kahonen, N, Sabin, M, Tossavainen, P, Jokinen, E, Laitinen, T, Viikari, J, Raitakari, OT, Juonala, M, Cuthbertson, DJ, Koskinen, J, Brown, E, Magnussen, CG, Hutri-Kahonen, N, Sabin, M, Tossavainen, P, Jokinen, E, Laitinen, T, Viikari, J, Raitakari, OT, and Juonala, M

Abstract

AIMS: To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up. METHODS: At baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m2), overweight (≥25-<30 kg/m2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI. RESULTS: 514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups. CONCLUSIONS: An increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a signifi

Published
2021

9. Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)

Author

Cuthbertson, D. J. (Daniel J.), Koskinen, J. (Juha), Brown, E. (Emily), Magnussen, C. G. (Costan G.), Hutri-Kähönen, N. (Nina), Sabin, M. (Matthew), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Laitinen, T. (Tomi), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), Juonalaj, M. (Markus), Cuthbertson, D. J. (Daniel J.), Koskinen, J. (Juha), Brown, E. (Emily), Magnussen, C. G. (Costan G.), Hutri-Kähönen, N. (Nina), Sabin, M. (Matthew), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Laitinen, T. (Tomi), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), and Juonalaj, M. (Markus)

Abstract

Aims: To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up. Methods: At baseline (in 2001) 2020 participants, males and females, aged 24–39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m²), overweight (≥25–<30 kg/m²), or obese (≥30 kg/m²) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI. Results: 514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9–10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups. Conclusions: An increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.

Published
2021

10. Association between number of siblings and cardiovascular risk factors in childhood and in adulthood:the Cardiovascular Risk in Young Finns Study

Author

Pihlman, J. (Jukka), Magnussen, C. G. (Costan G.), Rovio, S. P. (Suvi P.), Pahkala, K. (Katja), Jokinen, E. (Eero), Laitinen, T. P. (Tomi P.), Hutri-Kähönen, N. (Nina), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Kähönen, M. (Mika), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Juonala, M. (Markus), Nuotio, J. (Joel), Pihlman, J. (Jukka), Magnussen, C. G. (Costan G.), Rovio, S. P. (Suvi P.), Pahkala, K. (Katja), Jokinen, E. (Eero), Laitinen, T. P. (Tomi P.), Hutri-Kähönen, N. (Nina), Tossavainen, P. (Päivi), Taittonen, L. (Leena), Kähönen, M. (Mika), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Juonala, M. (Markus), and Nuotio, J. (Joel)

Abstract

Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3–18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m², 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m², 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m², 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention.

Published
2021

11. Influence of early-life body mass index and systolic blood pressure on left ventricle in adulthood:the Cardiovascular Risk in Young Finns Study

Author

Heiskanen, J. S. (Jarkko S.), Hernesniemi, J. A. (Jussi A.), Ruohonen, S. (Saku), Hutri-Kähönen, N. (Nina), Kähönen, M. (Mika), Jokinen, E. (Eero), Tossavainen, P. (Päivi), Kallio, M. (Merja), Laitinen, T. (Tomi), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Juonala, M. (Markus), Nevalainen, J. (Jaakko), Raitakari, O. T. (Olli T.), Heiskanen, J. S. (Jarkko S.), Hernesniemi, J. A. (Jussi A.), Ruohonen, S. (Saku), Hutri-Kähönen, N. (Nina), Kähönen, M. (Mika), Jokinen, E. (Eero), Tossavainen, P. (Päivi), Kallio, M. (Merja), Laitinen, T. (Tomi), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Juonala, M. (Markus), Nevalainen, J. (Jaakko), and Raitakari, O. T. (Olli T.)

Abstract

Background: Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. Methods: We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6–18) BMI and SPB on LVM in an adult population (N = 1864, aged 34–49). The burden of early-life BMI and SBP was defined as area under the curve. Results: After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 − 5.28], p < 0.001). Overweight in early-life (age- and sex-specific BMI values corresponding to adult BMI > 25 kg/m²) associated with 4.7% (2.5–6.9%, p < 0.0001) higher LVM regardless of BMI status in adulthood. Overweight in early-life combined with obesity in adulthood (BMI > 30kg/m²) resulted in a 21% (17.3–32.9%, p < 0.0001) increase in LVM. Higher early-life BMI was associated with a risk of developing eccentric hypertrophy. The burden of early-life SPB was not associated with adult LVM or left ventricular remodeling. Conclusions: High BMI in early-life confers a sustained effect on LVM and the risk for eccentric hypertrophy independently of adulthood risk factors.

Published
2021

14. Childhood Exposure to Parental Smoking and Midlife Cognitive Function The Young Finns Study

Author

Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, and Children's Hospital

Subjects
SECONDHAND SMOKE, parental smoking, passive smoking, NICOTINE EXPOSURE, Cambridge Neuropsychological Test Automated Battery, ADULTHOOD, PERFORMANCE, 3142 Public health care science, environmental and occupational health, COTININE, AGE, CIGARETTE-SMOKE, SELF-REPORTED SMOKING, CARDIOVASCULAR RISK-FACTORS, OXIDATIVE STRESS, tobacco smoke, cognitive function, secondhand smoke
Abstract

We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine

Published
2020

15. Childhood socioeconomic disadvantage and risk of fatty liver in adulthood:the cardiovascular risk in young Finns study

Author

Laitinen, T. T. (Tomi T.), Vahtera, J. (Jussi), Pahkala, K. (Katja), Magnussen, C. G. (Costan G.), Nuotio, J. (Joel), Hutri-Kähönen, N. (Nina), Kivimäki, M. (Mika), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Tossavainen, P. (Päivi), Pentti, J. (Jaana), Viikari, J. S. (Jorma S.A.), Juonala, M. (Markus), and Raitakari, O. T. (Olli T.)

Abstract

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3‐18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow‐up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents’ socioeconomic position and socioeconomic circumstances in participants’ residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow‐up (2011) at ages 34‐49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18‐1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09‐1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.

Published
2020

19. Childhood exposure to parental smoking and midlife cognitive function:the Young Finns Study

Author

Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), Raitakari, O. T. (Olli T.), Rovio, S. P. (Suvi P.), Pihlman, J. (Jukka), Pahkala, K. (Katja), Juonala, M. (Markus), Magnussen, C. G. (Costan G.), Pitkänen, N. (Niina), Ahola-Olli, A. (Ari), Salo, P. (Pia), Kähönen, M. (Mika), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Jokinen, E. (Eero), Laitinen, T. (Tomi), Taittonen, L. (Leena), Tossavainen, P. (Päivi), Viikari, J. S. (Jorma S. A.), and Raitakari, O. T. (Olli T.)

Abstract

We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine <1.0 ng/mL); 2) hygienic parental smoking (1–2 smoking parents, cotinine <1.0 ng/mL); and 3) nonhygienic parental smoking (1–2 smoking parents, cotinine ≥1.0 ng/mL). Analyses adjusted for sex, age, family socioeconomic status, polygenic risk score for cognitive function, adolescent/adult smoking, blood pressure, and serum total cholesterol level. Compared with the nonexposed, participants exposed to nonhygienic parental smoking were at higher risk of poor (lowest quartile) midlife episodic memory and associative learning (relative risk (RR) = 1.38, 95% confidence interval (CI): 1.08, 1.75), and a weak association was found for short-term and spatial working memory (RR = 1.25, 95% CI: 0.98, 1.58). Associations for those exposed to hygienic parental smoking were nonsignificant (episodic memory and associative learning: RR = 1.19, 95% CI: 0.92, 1.54; short-term and spatial working memory: RR = 1.10, 95% CI: 0.85, 1.34). We conclude that avoiding childhood/adolescence secondhand smoke exposure promotes adulthood cognitive function.

Published
2020

20. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults:the cardiovascular risk in Young Finns study

Author

Hunjadi, M. (Monika), Lamina, C. (Claudia), Kahler, P. (Patrick), Bernscherer, T. (Tamara), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Hurme, M. (Mikko), Juonala, M. (Markus), Taittonen, L. (Leena), Laitinen, T. (Tomi), Jokinen, E. (Eero), Tossavainen, P. (Päivi), Hutri-Kähönen, N. (Nina), Raitakari, O. (Olli), Ritsch, A. (Andreas), Hunjadi, M. (Monika), Lamina, C. (Claudia), Kahler, P. (Patrick), Bernscherer, T. (Tamara), Viikari, J. (Jorma), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Hurme, M. (Mikko), Juonala, M. (Markus), Taittonen, L. (Leena), Laitinen, T. (Tomi), Jokinen, E. (Eero), Tossavainen, P. (Päivi), Hutri-Kähönen, N. (Nina), Raitakari, O. (Olli), and Ritsch, A. (Andreas)

Abstract

The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated ³H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young’s modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis.

Published
2020

21. Childhood risk factors and carotid atherosclerotic plaque in adulthood:the cardiovascular risk in Young Finns Study

Author

Koskinen, J. S. (Juhani S.), Kytö, V. (Ville), Juonala, M. (Markus), Viikari, J. S. (Jorma S. A.), Nevalainen, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Hutri-Kähönen, N. (Nina), Laitinen, T. (Tomi), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Magnussen, C. G. (Costan G.), Raitakari, O. T. (Olli T.), Koskinen, J. S. (Juhani S.), Kytö, V. (Ville), Juonala, M. (Markus), Viikari, J. S. (Jorma S. A.), Nevalainen, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Hutri-Kähönen, N. (Nina), Laitinen, T. (Tomi), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Magnussen, C. G. (Costan G.), and Raitakari, O. T. (Olli T.)

Abstract

Background and aims: Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. Methods: The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3—18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6—18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. Results: Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen <50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76—5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99—2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26—2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. Conclusions: Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

Published
2020

33. Longitudinal analysis of risk of non-alcoholic fatty liver disease in adulthood

Author

Cuthbertson, DJ, Brown, E, Koskinen, J, Magnussen, CG, Hutri-Kahonen, N, Sabin, M, Tossavainen, P, Jokinen, E, Laitinen, T, Viikari, J, Raitakari, OT, Juonala, M, Cuthbertson, DJ, Brown, E, Koskinen, J, Magnussen, CG, Hutri-Kahonen, N, Sabin, M, Tossavainen, P, Jokinen, E, Laitinen, T, Viikari, J, Raitakari, OT, and Juonala, M

Abstract

BACKGROUND & AIMS: We aimed to determine how childhood body mass index and metabolic health, along with the change in body mass index between childhood and adulthood, determine the risk of adult non-alcoholic fatty liver disease. METHODS: Data from 2020 participants aged 3-18 years at baseline, followed up 31 years later, were examined to assess the utility of four childhood metabolic phenotypes (Metabolic Groups I: normal body mass index, no metabolic disturbances; II: normal body mass index, one or more metabolic disturbances; III: overweight/obese, no metabolic disturbances; IV: overweight/obese, one or more metabolic disturbances) and four life-course adiposity phenotypes (Adiposity Group 1: normal child and adult body mass index; 2, high child, normal adult body mass index; 3, normal child body mass index, high adult body mass index; 4, high child and adult body mass index) in predicting adult non-alcoholic fatty liver disease. RESULTS: The risk for adult non-alcoholic fatty liver disease was similar across all four groups after adjustment for age, sex, lifestyle factors and adult body mass index. Risk of adult non-alcoholic fatty liver disease was not increased among individuals overweight/obese in childhood but non-obese in adulthood. In contrast, overweight or obese adults, irrespective of their youth body mass index status, had ~eight-fold to 10-fold increased risk (P < 0.001). CONCLUSIONS: Childhood overweight/obesity, not metabolic health, is associated with increased risk for adult non-alcoholic fatty liver disease. However, the increased risk associated with childhood overweight/obesity can be largely removed by obtaining a normal body mass index by adulthood.

Published
2019

34. Longitudinal analysis of risk of non-alcoholic fatty liver disease in adulthood

Author

Cuthbertson, D. J. (Daniel J.), Brown, E. (Emily), Koskinen, J. (Juha), Magnussen, C. G. (Costan G.), Hutri‐Kähönen, N. (Nina), Sabin, M. (Matthew), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Laitinen, T. (Tomi), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), Juonala, M. (Markus), Cuthbertson, D. J. (Daniel J.), Brown, E. (Emily), Koskinen, J. (Juha), Magnussen, C. G. (Costan G.), Hutri‐Kähönen, N. (Nina), Sabin, M. (Matthew), Tossavainen, P. (Päivi), Jokinen, E. (Eero), Laitinen, T. (Tomi), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), and Juonala, M. (Markus)

Abstract

Background & Aims: We aimed to determine how childhood body mass index and metabolic health, along with the change in body mass index between childhood and adulthood, determine the risk of adult non‐alcoholic fatty liver disease. Methods: Data from 2020 participants aged 3–18 years at baseline, followed up 31 years later, were examined to assess the utility of four childhood metabolic phenotypes (Metabolic Groups I: normal body mass index, no metabolic disturbances; II: normal body mass index, one or more metabolic disturbances; III: overweight/obese, no metabolic disturbances; IV: overweight/obese, one or more metabolic disturbances) and four life‐course adiposity phenotypes (Adiposity Group 1: normal child and adult body mass index; 2, high child, normal adult body mass index; 3, normal child body mass index, high adult body mass index; 4, high child and adult body mass index) in predicting adult non‐alcoholic fatty liver disease. Results: The risk for adult non‐alcoholic fatty liver disease was similar across all four groups after adjustment for age, sex, lifestyle factors and adult body mass index. Risk of adult non‐alcoholic fatty liver disease was not increased among individuals overweight/obese in childhood but non‐obese in adulthood. In contrast, overweight or obese adults, irrespective of their youth body mass index status, had ~eight‐fold to 10‐fold increased risk (P < 0.001). Conclusions: Childhood overweight/obesity, not metabolic health, is associated with increased risk for adult non‐alcoholic fatty liver disease. However, the increased risk associated with childhood overweight/obesity can be largely removed by obtaining a normal body mass index by adulthood.

Published
2019

38. The implementation of a nationwide anomaly screening programme improves prenatal detection of major cardiac defects: an 11‐year national population‐based cohort study

Author

Hautala, J, primary, Gissler, M, additional, Ritvanen, A, additional, Tekay, A, additional, Pitkänen‐Argillander, O, additional, Stefanovic, V, additional, Sarkola, T, additional, Helle, E, additional, Pihkala, J, additional, Pätilä, T, additional, Mattila, IP, additional, Jokinen, E, additional, Räsänen, J, additional, and Ojala, T, additional

Published
2019
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39. BMI trajectories associated with resolution of elevated youth BMI and incident adult obesity.

Author

Tossavainen P., Jokinen E., Laitinen T., Hutri-Kahonen N., Magnussen C.G., Raitakari O.T., Buscot M.-J., Thomson R.J., Juonala M., Sabin M.A., Burgner D.P., Lehtimaki T., Viikari J.S.A., Tossavainen P., Jokinen E., Laitinen T., Hutri-Kahonen N., Magnussen C.G., Raitakari O.T., Buscot M.-J., Thomson R.J., Juonala M., Sabin M.A., Burgner D.P., Lehtimaki T., and Viikari J.S.A.

Abstract

Background and Objectives: Youth with high BMI who become nonobese adults have the same cardiovascular risk factor burden as those who were never obese. However, the early-life BMI trajectories for overweight or obese youth who avoid becoming obese adults have not been described. We aimed to determine and compare the young-childhood BMI trajectories of participants according to their BMI status in youth and adulthood. Method(s): Bayesian hierarchical piecewise regression modeling was used to analyze the BMI trajectories of 2717 young adults who had up to 8 measures of BMI from childhood (ages 3-18 years) to adulthood (ages 34-49 years). Result(s): Compared with those with persistently high BMI, those who resolved their high youth BMI by adulthood had lower average BMI at age 6 years and slower rates of BMI change from young childhood. In addition, their BMI levels started to plateau at 16 years old for females and 21 years old for males, whereas the BMI of those whose high BMI persisted did not stabilize until 25 years old for male subjects and 27 years for female subjects. Compared with those youth who were not overweight or obese and who remained nonobese in adulthood, those who developed obesity had a higher BMI rate of change from 6 years old, and their BMI continued to increase linearly until age 30 years. Conclusion(s): Efforts to alter BMI trajectories for adult obesity should ideally commence before age 6 years. The natural resolution of high BMI starts in adolescence for males and early adulthood for females, suggesting a critical window for secondary prevention.Copyright © 2018 by the American Academy of Pediatrics. All rights reserved.

Published
2018

40. Suomen perinteiset vähemmistöt peruskoulun oppikirjoissa

Author

Jokinen, E. (Essi)

Subjects
Geography
Abstract

Pro gradu -tutkielma tarkastelee, miten Suomen perinteisiä vähemmistöjä käsitellään maantiedon, yhteiskuntaopin, uskonnon ja elämänkatsomustiedon oppikirjoissa. Oppikirjat perustuvat vuoden 2004 peruskoulun opetussuunnitelmaan. Tutkimuksen tarkoituksena on selvittää, mitä perinteisiä vähemmistöjä oppikirjoissa esiintyy, minkälaisen kuvan kirjat luovat vähemmistöistä ja minkälaisena vähemmistöjen identiteetti esiintyy suhteessa suomalaiseen identiteettiin. Tutkimuksessa tarkastellaan myös enemmistön ja vähemmistöjen välisiä valtasuhteita. Periteisillä vähemmistöillä tarkoitetaan Suomessa pitkään eläneitä kulttuuri- ja kielivähemmistöryhmiä: saamelaisia, suomenruotsalaisia, romaneja, venäläisiä ja tataareja. Tutkimus on tehty tarkastelemalla 13 peruskoulun oppikirjan tekstejä ja kuvia sisällönanalyysin keinoin. Oppikirjoista on etsitty asioita, jotka liittyvät vähemmistöjen määritelmään, kokoon, kieleen, historiaan, asemaan sekä kulttuurin piirteisiin ja tapoihin. Sisältöjä on tarkasteltu kriittisesti ja syvällisesti, jotta niistä on pystytty löytämään merkityksiä. Tutkimustuloksia on yhdistetty teoriassa esiintyviin aiheisiin, joita ovat muun muassa monikulttuurisuus, valtasuhteet, nationalismi, toiseus ja oppikirjojen merkitys opetuksessa. Teorian ja tulosten avulla on tarkasteltu niitä prosesseja, jotka vaikuttavat oppikirjojen sisältöjen taustalla, ja joita tulisi tunnistaa objektiivisen ja kaikkia palvelevan opetuksen ylläpitämiseksi. Tulosten mukaan oppikirjat käsittelevät vähemmistöjä stereotyyppisesti ja yksinkertaistaen. Vähemmistöt esitellään myös aina omissa erillisissä luvuissaan, mikä korostaa eroa vähemmistöjen ja enemmistön välillä. Vähemmistöt erotellaan oppikirjojen sisällöissä eri tavoin. Saamelaiset ja romanit erotetaan suomalaisista vahvemmin kuin suomenruotsalaiset, venäläiset ja tataarit. Yleensä erottelu perustuu kieleen, kulttuuriin ja tapoihin tai etnisyyteen. Oppikirjat ovat vaiheessa, jossa oma suomalainen kulttuuri nähdään muita kulttuureja merkityksellisempänä. Oppikirjoja voidaan kehittää välittämään tasa-arvoisempaa ja monikulttuurisempaa kuvaa Suomesta. Tällöin täytyy kiinnittää huomiota niihin rakenteisiin, jotka luovat oppikirjoissa eriarvoisuutta. Tätä voi edistää oppikirjoja tarkastelevalla tutkimuksella ja saattamalla saadut tutkimustulokset myös opettajien ja oppikirjojen tekijöiden tietoon.

Published
2017

42. Cardiovascular pre-participation screening in young athletes: Recommendations of the Association of European Paediatric Cardiology.

Author

Fritsch P, Ehringer-Schetitska D, Dalla Pozza R, Jokinen E, Herceg V, Hidvegi E, Petropoulos A, Oberhoffer R on behalf of the Association for European Paediatric Cardiology Working Group Cardiovascular Prevention and Fritsch P, Ehringer-Schetitska D, Dalla Pozza R, Jokinen E, Herceg V, Hidvegi E, Petropoulos A, Oberhoffer R on behalf of the Association for European Paediatric Cardiology Working Group Cardiovascular Prevention

Published
2017

43. Perusta taiteesta:taideperustaisuus lastentarhanopettajan pedagogisen osaamisen vahvistajana

Author

Korhonen-Jokinen, E.-M. (Eeva-Maria) and Korhonen-Jokinen, E.-M. (Eeva-Maria)

Abstract

Tutkielman tavoitteena on selvittää taideperustaisia lähestymistapoja, jotka voisivat vahvistaa lastentarhanopettajan pedagogista osaamista. Tutkielman myötä haluan kehittää omaa ammattijuuttani lastentarhanopettajana ja kuvataiteilijana. Tutkielma on narratiivisen kuvailevan kirjallisuuskatsauksen periaatteita noudattava teoreettinen synteesi taideperustaisuudesta. Lähestyn aihetta lastentarhanopettajan pedagogisen osaamisen vahvistamisen kannalta. Aineisto muodostuu suomen- ja englanninkielisestä kirjallisuudesta ja verkkolähteistä. Tutkimuskysymykseni on, miten taideperustaisuus voi vahvistaa lastentarhanopettajan pedagogista osaamista. Lisäksi kysyn, mitä taideperustaisuus pitää sisällään ja miten lastentarhanopettajan pedagoginen osaaminen määritellään. Taideperustaisen tutkimuksen lähtökohtia ovat holistinen ihmiskäsitys ja näkemys taiteesta tietoa todellisuudesta tuottavana. Peilaan tutkielmassani taideperustaisuutta Rauhalan holistiseen ihmiskäsitykseen (1983) ja Kolbin kokemuksellisen oppimisen teoriaan (1984). Lastentarhanopettajan pedagoginen ja laaja-alainen osaaminen perustuvat tutkielmassani Opetusalan ammattijärjestön ja Lastentarhanopettajaliiton määritelmiin lastentarhanopettajan työhön kuuluvista työvälineistä ja laaja-alaisesta osaamisesta. Tutkielman viitekehykseen kuuluu myös Varhaiskasvatussuunnitelman perusteet (2016). Taideperustainen tutkimus ja kasvatus sekä taidelähtöiset menetelmät muodostavat toisiinsa kietoutuvan ajatusmallin. Pyrkimyksenä niissä on taiteelliseen ilmaisuun perustuvan sekä tutkimuksellisen asenteen yhdistävän ja yhteisöllisen toiminnan kautta löytää erilaisia vuorovaikutuksen keinoja sekä yhteyttä itseen ja toiseen. Toiminnassa oleellista on prosessi, ei lopputuotos. Lastentarhanopettajan pedagoginen osaaminen muodostuu koulutuksen ja käytännön työn kautta kehittyneestä laaja-alaisesta osaamisesta. Siihen kuuluvat myös ilmaisu- ja taidekasvatuksen monipuolinen osaaminen. Lastentarhanopettaja voi pienin keinoin sisällyttä

Published
2017

46. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, J.S. (Janina), Jeff, J. (Janina), Chu, A.Y. (Audrey Y), Bragg-Gresham, J.L. (Jennifer L.), Dongen, J. (Jenny) van, Huffman, J.E. (Jennifer), Ahluwalia, T.S. (Tarunveer Singh), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Jackson, A.U. (Anne), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Luan, J. (Jian'An), Mägi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, M.C. (Carolina), Monda, K.L. (Keri), Nolte, I.M. (Ilja), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L.M. (Lynda), Salvi, E. (Erika), Smith, M.T. (Megan T.), Snieder, H. (Harold), Standáková, A. (Alena), Ju Sung, Y. (Yun), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Harst, P. (Pim) van der, Walker, R.W. (Ryan W.), Wang, S.R. (Sophie), Wild, S.H. (Sarah), Willems, S.M. (Sara), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Couto-Alves, A. (Alexessander), Bakker, S.J.L. (Stephan), Barlassina, C. (Cristina), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bellis, C. (Claire), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Blangero, J. (John), Blüher, M. (Matthias), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan R.), Bruinenberg, M. (M.), Campbell, H. (Harry), Chen, Y.-D.I. (Yii-Der Ida), Chiang, C.W.K. (Charleston W. K.), Chines, P.S. (Peter), Collins, F.S. (Francis), Cucca, F. (Fracensco), Cupples, L.A. (Adrienne), D'avila, F. (Francesca), Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Dimitriou, M. (Maria), Döring, A. (Angela), Hagen, K. (Knut), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gjesing, A.P. (Anette), Glorioso, N. (Nicola), Graff, M.J. (Maud J.L.), Grallert, H. (Harald), Grarup, N. (Niels), Gräßler, J. (Jürgen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M.N. (Marie Neergaard), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Havulinna, A.S. (Aki), Heliovaara, M. (Markku), Hillege, H.L. (Hans), Hofman, A. (Albert), Holmen, O.L. (Oddgeir), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Hui, J. (Jennie), Husemoen, L.L.N. (Lise Lotte), Hysi, P.G. (Pirro), Isaacs, A.J. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. (Alan), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Marie Justesen, J. (Johanne), Justice, A.E. (Anne), Kähönen, M. (Mika), Karaleftheri, M. (Maria), Tee Khaw, K. (Kay), Keinanen-Kiukaanniemi, S. (Sirkka), Kinnunen, L. (Leena), Knekt, P., Koistinen, H. (Heikki), Kolcic, I. (Ivana), Kooner, I.K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. (Alex), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia), Lindström, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Manunta, P. (Paolo), Leach, I.M. (Irene Mateo), McArdle, W.L. (Wendy), Mcknight, B. (Barbara), Mohlke, K.L. (Karen), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M.E. (May E.), Morris, A.P. (Andrew), Müller, G. (Gabriele), Musk, A.W. (Arthur W.), Narisu, N. (Narisu), Ong, K.K. (Ken K.), Oostra, B.A. (Ben), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J.S. (James), Paternoster, L. (Lavinia), Penninx, B.W.J.H. (Brenda), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C., Rayner, N.W. (Nigel William), Ribel-Madsen, R. (Rasmus), Rice, T.K. (Treva K.), Richards, M. (Marcus), Ridker, P.M. (Paul), Rivadeneira Ramirez, F. (Fernando), Ryan, K.A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparsø, T. (Thomas), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Swertz, M. (Morris), Swift, A.J. (Amy), Tönjes, A. (Anke), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. (Jorma), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waeber, G. (Gérard), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Winkler, T.W. (Thomas W.), Wright, A.F. (Alan), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Chambers, J.C. (John), Chasman, D.I. (Daniel), Cusi, D. (Daniele), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Hansen, T. (T.), Hicks, A.A. (Andrew), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Metspalu, A. (Andres), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Palmer, L.J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B.M. (Bruce), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Shudiner, A.R. (Alan R.), Smit, J.H. (Jan), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Völker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Zeggini, E. (Eleftheria), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Duijn, C.M. (Cornelia) van, Fox, C.S. (Caroline), Groop, L. (Leif), Heid, I.M. (Iris), Hunter, D.J. (David J.), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark), North, K.E. (Kari), O´Connell, J.R., Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D.P. (David), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Müller-Nurasyid, M. (Martina), Loos, R.J.F. (Ruth), Ried, J.S. (Janina), Jeff, J. (Janina), Chu, A.Y. (Audrey Y), Bragg-Gresham, J.L. (Jennifer L.), Dongen, J. (Jenny) van, Huffman, J.E. (Jennifer), Ahluwalia, T.S. (Tarunveer Singh), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Jackson, A.U. (Anne), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Luan, J. (Jian'An), Mägi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, M.C. (Carolina), Monda, K.L. (Keri), Nolte, I.M. (Ilja), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L.M. (Lynda), Salvi, E. (Erika), Smith, M.T. (Megan T.), Snieder, H. (Harold), Standáková, A. (Alena), Ju Sung, Y. (Yun), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Harst, P. (Pim) van der, Walker, R.W. (Ryan W.), Wang, S.R. (Sophie), Wild, S.H. (Sarah), Willems, S.M. (Sara), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Couto-Alves, A. (Alexessander), Bakker, S.J.L. (Stephan), Barlassina, C. (Cristina), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bellis, C. (Claire), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Blangero, J. (John), Blüher, M. (Matthias), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan R.), Bruinenberg, M. (M.), Campbell, H. (Harry), Chen, Y.-D.I. (Yii-Der Ida), Chiang, C.W.K. (Charleston W. K.), Chines, P.S. (Peter), Collins, F.S. (Francis), Cucca, F. (Fracensco), Cupples, L.A. (Adrienne), D'avila, F. (Francesca), Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Dimitriou, M. (Maria), Döring, A. (Angela), Hagen, K. (Knut), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gjesing, A.P. (Anette), Glorioso, N. (Nicola), Graff, M.J. (Maud J.L.), Grallert, H. (Harald), Grarup, N. (Niels), Gräßler, J. (Jürgen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M.N. (Marie Neergaard), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Havulinna, A.S. (Aki), Heliovaara, M. (Markku), Hillege, H.L. (Hans), Hofman, A. (Albert), Holmen, O.L. (Oddgeir), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Hui, J. (Jennie), Husemoen, L.L.N. (Lise Lotte), Hysi, P.G. (Pirro), Isaacs, A.J. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. (Alan), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Marie Justesen, J. (Johanne), Justice, A.E. (Anne), Kähönen, M. (Mika), Karaleftheri, M. (Maria), Tee Khaw, K. (Kay), Keinanen-Kiukaanniemi, S. (Sirkka), Kinnunen, L. (Leena), Knekt, P., Koistinen, H. (Heikki), Kolcic, I. (Ivana), Kooner, I.K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. (Alex), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia), Lindström, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Manunta, P. (Paolo), Leach, I.M. (Irene Mateo), McArdle, W.L. (Wendy), Mcknight, B. (Barbara), Mohlke, K.L. (Karen), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M.E. (May E.), Morris, A.P. (Andrew), Müller, G. (Gabriele), Musk, A.W. (Arthur W.), Narisu, N. (Narisu), Ong, K.K. (Ken K.), Oostra, B.A. (Ben), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J.S. (James), Paternoster, L. (Lavinia), Penninx, B.W.J.H. (Brenda), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C., Rayner, N.W. (Nigel William), Ribel-Madsen, R. (Rasmus), Rice, T.K. (Treva K.), Richards, M. (Marcus), Ridker, P.M. (Paul), Rivadeneira Ramirez, F. (Fernando), Ryan, K.A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparsø, T. (Thomas), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Swertz, M. (Morris), Swift, A.J. (Amy), Tönjes, A. (Anke), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. (Jorma), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waeber, G. (Gérard), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Winkler, T.W. (Thomas W.), Wright, A.F. (Alan), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Chambers, J.C. (John), Chasman, D.I. (Daniel), Cusi, D. (Daniele), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Hansen, T. (T.), Hicks, A.A. (Andrew), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Metspalu, A. (Andres), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Palmer, L.J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B.M. (Bruce), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P.E.H. (Peter), Shudiner, A.R. (Alan R.), Smit, J.H. (Jan), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Völker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Zeggini, E. (Eleftheria), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Duijn, C.M. (Cornelia) van, Fox, C.S. (Caroline), Groop, L. (Leif), Heid, I.M. (Iris), Hunter, D.J. (David J.), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark), North, K.E. (Kari), O´Connell, J.R., Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D.P. (David), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Müller-Nurasyid, M. (Martina), and Loos, R.J.F. (Ruth)

Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

Published
2016
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47. Previous exposure to intact speech increases intelligibility of its digitally degraded counterpart as a function of stimulus complexity

Author

Hakonen, Maria, May, Patrick, Alho, Jussi, Alku, Paavo, Jokinen, E, Jääskeläinen, Iiro, Tiitinen, Hannu, Hakonen, Maria, May, Patrick, Alho, Jussi, Alku, Paavo, Jokinen, E, Jääskeläinen, Iiro, and Tiitinen, Hannu

Abstract

Recent studies have shown that acoustically distorted sentences can be perceived as either unintelligible or intelligible depending on whether one has previously been exposed to the undistorted, intelligible versions of the sentences. This allows studying processes specifically related to speech intelligibility since any change between the responses to the distorted stimuli before and after the presentation of their undistorted counterparts cannot be attributed to acoustic variability but, rather, to the successful mapping of sensory information onto memory representations. To estimate how the complexity of the message is reflected in speech comprehension, we applied this rapid change in perception to behavioral and magnetoencephalography (MEG) experiments using vowels, words and sentences. In the experiments, stimuli were initially presented to the subject in a distorted form, after which undistorted versions of the stimuli were presented. Finally, the original distorted stimuli were presented once more. The resulting increase in intelligibility observed for the second presentation of the distorted stimuli depended on the complexity of the stimulus: vowels remained unintelligible (behaviorally measured intelligibility 27%) whereas the intelligibility of the words increased from 19% to 45% and that of the sentences from 31% to 65%. This increase in the intelligibility of the degraded stimuli was reflected as an enhancement of activity in the auditory cortex and surrounding areas at early latencies of 130–160 ms. In the same regions, increasing stimulus complexity attenuated mean currents at latencies of 130–160 ms whereas at latencies of 200–270 ms the mean currents increased. These modulations in cortical activity may reflect feedback from top-down mechanisms enhancing the extraction of information from speech. The behavioral results suggest that memory-driven expectancies can have a significant effect on speech comprehension, especially in acoustically adverse con

Published
2016

48. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, J. S. (Janina S.), Jeff, J. M. (Janina M.), Chu, A. Y. (Audrey Y.), Bragg-Gresham, J. L. (Jennifer L.), van Dongen, J. (Jenny), Huffman, J. E. (Jennifer E.), Ahluwalia, T. S. (Tarunveer S.), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tonu), Feitosa, M. F. (Mary F.), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N. L. (Nancy L.), Jackson, A. U. (Anne U.), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltan), Lahti, J. (Jari), Luan, J. (Jian'an), Maegi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, C. (Carolina), Monda, K. L. (Keri L.), Nolte, I. M. (Ilja M.), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L. M. (Lynda M.), Salvi, E. (Erika), Smith, M. T. (Megan T.), Snieder, H. (Harold), Stancakova, A. (Alena), Sung, Y. J. (Yun Ju), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), van der Harst, P. (Pim), Walker, R. W. (Ryan W.), Wang, S. R. (Sophie R.), Wild, S. H. (Sarah H.), Willems, S. M. (Sara M.), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Alves, A. C. (Alexessander Couto), Bakker, S. J. (Stephan J. L.), Barlassina, C. (Cristina), Bartz, T. M. (Traci M.), Beilby, J. (John), Bellis, C. (Claire), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Blangero, J. (John), Blueher, M. (Matthias), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bruinenberg, M. (Marcel), Campbell, H. (Harry), Chen, Y. I. (Yii-Der Ida), Chiang, C. W. (Charleston W. K.), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Cucca, F. (Fracensco), Cupples, L. A. (L. Adrienne), D'Avila, F. (Francesca), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Dimitriou, M. (Maria), Doering, A. (Angela), Eriksson, J. G. (Johan G.), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N. G. (Nita G.), Friedrich, N. (Nele), Gjesing, A. P. (Anette Prior), Glorioso, N. (Nicola), Graff, M. (Mariaelisa), Grallert, H. (Harald), Grarup, N. (Niels), Graessler, J. (Juergen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M. N. (Marie Neergaard), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nicholas), Hattersley, A. T. (Andrew Tym), Havulinna, A. S. (Aki S.), Heliovaara, M. (Markku), Hillege, H. (Hans), Hofman, A. (Albert), Holmen, O. (Oddgeir), Homuth, G. (Georg), Hottenga, J.-J. (Jouke-Jan), Hui, J. (Jennie), Husemoen, L. L. (Lise Lotte), Hysi, P. G. (Pirro G.), Isaacs, A. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. L. (Alan L.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Justesen, J. M. (Johanne Marie), Justice, A. E. (Anne E.), Kahonen, M. (Mika), Karaleftheri, M. (Maria), Khaw, K. T. (Kay Tee), Keinänen-Kiukaanniemi, S. M. (Sirkka M.), Kinnunen, L. (Leena), Knekt, P. B. (Paul B.), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kooner, I. K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. M. (Alexandra M.), Lichtner, P. (Peter), Lindgren, C. M. (Cecilia M.), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R. (Robert), Lyssenko, V. (Valeriya), Mannisto, S. (Satu), Manunta, P. (Paolo), Leach, I. M. (Irene Mateo), McArdle, W. L. (Wendy L.), Mcknight, B. (Barbara), Mohlke, K. L. (Karen L.), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M. E. (May E.), Morris, A. P. (Andrew P.), Mueller, G. (Gabriele), Musk, A. W. (Arthur W.), Narisu, N. (Narisu), Ong, K. K. (Ken K.), Oostra, B. A. (Ben A.), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J. S. (James S.), Paternoster, L. (Lavinia), Penninx, B. W. (Brenda W.), Pichler, I. (Irene), Pilia, M. G. (Maria G.), Polasek, O. (Ozren), Pramstaller, P. P. (Peter P.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rayner, N. W. (Nigel W.), Ribel-Madsen, R. (Rasmus), Rice, T. K. (Treva K.), Richards, M. (Marcus), Ridker, P. M. (Paul M.), Rivadeneira, F. (Fernando), Ryan, K. A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Scholtens, S. (Salome), Scott, R. A. (Robert A.), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparso, T. H. (Thomas Hempel), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathleen), Stolk, R. P. (Ronald P.), Strauch, K. (Konstantin), Stringham, H. M. (Heather M.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Toenjes, A. (Anke), Tsafantakis, E. (Emmanouil), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. S. (Jorma S.), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Widen, E. (Elisabeth), Willemsen, G. (Gonneke), Wilsgaard, T. (Tom), Winkler, T. W. (Thomas W.), Wright, A. F. (Alan F.), Yerges-Armstrong, L. M. (Laura M.), Zhao, J. H. (Jing Hua), Zillikens, M. C. (M. Carola), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Cusi, D. (Daniele), Gansevoort, R. T. (Ron T.), Gieger, C. (Christian), Hansen, T. (Torben), Hicks, A. A. (Andrew A.), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Lehtimaeki, T. (Terho), Metspalu, A. (Andres), Njolstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A. J. (Albertine J.), Palmer, L. J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P. E. (Peter E. H.), Shudiner, A. R. (Alan R.), Smit, J. H. (Jan H.), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Timothy D.), Stefansson, K. (Kari), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Voelker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Wilson, J. F. (James F.), Zeggini, E. (Eleftheria), Abecasis, G. R. (Goncalo R.), Boehnke, M. (Michael), Borecki, I. B. (Ingrid B.), Deloukas, P. (Panos), van Duijn, C. M. (Cornelia M.), Fox, C. (Caroline), Groop, L. C. (Leif C.), Heid, I. M. (Iris M.), Hunter, D. J. (David J.), Kaplan, R. C. (Robert C.), McCarthy, M. I. (Mark I.), North, K. E. (Kari E.), O'Connell, J. R. (Jeffrey R.), Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D. P. (David P.), Frayling, T. (Timothy), Hirschhorn, J. N. (Joel N.), Mueller-Nurasyid, M. (Martina), Loos, R. J. (Ruth J. F.), Ried, J. S. (Janina S.), Jeff, J. M. (Janina M.), Chu, A. Y. (Audrey Y.), Bragg-Gresham, J. L. (Jennifer L.), van Dongen, J. (Jenny), Huffman, J. E. (Jennifer E.), Ahluwalia, T. S. (Tarunveer S.), Cadby, G. (Gemma), Eklund, N. (Niina), Eriksson, J. (Joel), Esko, T. (Tonu), Feitosa, M. F. (Mary F.), Goel, A. (Anuj), Gorski, M. (Mathias), Hayward, C. (Caroline), Heard-Costa, N. L. (Nancy L.), Jackson, A. U. (Anne U.), Jokinen, E. (Eero), Kanoni, S. (Stavroula), Kristiansson, K. (Kati), Kutalik, Z. (Zoltan), Lahti, J. (Jari), Luan, J. (Jian'an), Maegi, R. (Reedik), Mahajan, A. (Anubha), Mangino, M. (Massimo), Medina-Gomez, C. (Carolina), Monda, K. L. (Keri L.), Nolte, I. M. (Ilja M.), Perusse, L. (Louis), Prokopenko, I. (Inga), Qi, L. (Lu), Rose, L. M. (Lynda M.), Salvi, E. (Erika), Smith, M. T. (Megan T.), Snieder, H. (Harold), Stancakova, A. (Alena), Sung, Y. J. (Yun Ju), Tachmazidou, I. (Ioanna), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), van der Harst, P. (Pim), Walker, R. W. (Ryan W.), Wang, S. R. (Sophie R.), Wild, S. H. (Sarah H.), Willems, S. M. (Sara M.), Wong, A. (Andrew), Zhang, W. (Weihua), Albrecht, E. (Eva), Alves, A. C. (Alexessander Couto), Bakker, S. J. (Stephan J. L.), Barlassina, C. (Cristina), Bartz, T. M. (Traci M.), Beilby, J. (John), Bellis, C. (Claire), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Blangero, J. (John), Blueher, M. (Matthias), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bruinenberg, M. (Marcel), Campbell, H. (Harry), Chen, Y. I. (Yii-Der Ida), Chiang, C. W. (Charleston W. K.), Chines, P. S. (Peter S.), Collins, F. S. (Francis S.), Cucca, F. (Fracensco), Cupples, L. A. (L. Adrienne), D'Avila, F. (Francesca), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Dimitriou, M. (Maria), Doering, A. (Angela), Eriksson, J. G. (Johan G.), Farmaki, A.-E. (Aliki-Eleni), Farrall, M. (Martin), Ferreira, T. (Teresa), Fischer, K. (Krista), Forouhi, N. G. (Nita G.), Friedrich, N. (Nele), Gjesing, A. P. (Anette Prior), Glorioso, N. (Nicola), Graff, M. (Mariaelisa), Grallert, H. (Harald), Grarup, N. (Niels), Graessler, J. (Juergen), Grewal, J. (Jagvir), Hamsten, A. (Anders), Harder, M. N. (Marie Neergaard), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nicholas), Hattersley, A. T. (Andrew Tym), Havulinna, A. S. (Aki S.), Heliovaara, M. (Markku), Hillege, H. (Hans), Hofman, A. (Albert), Holmen, O. (Oddgeir), Homuth, G. (Georg), Hottenga, J.-J. (Jouke-Jan), Hui, J. (Jennie), Husemoen, L. L. (Lise Lotte), Hysi, P. G. (Pirro G.), Isaacs, A. (Aaron), Ittermann, T. (Till), Jalilzadeh, S. (Shapour), James, A. L. (Alan L.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Justesen, J. M. (Johanne Marie), Justice, A. E. (Anne E.), Kahonen, M. (Mika), Karaleftheri, M. (Maria), Khaw, K. T. (Kay Tee), Keinänen-Kiukaanniemi, S. M. (Sirkka M.), Kinnunen, L. (Leena), Knekt, P. B. (Paul B.), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kooner, I. K. (Ishminder K.), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyriakou, T. (Theodosios), Laitinen, T. (Tomi), Langenberg, C. (Claudia), Lewin, A. M. (Alexandra M.), Lichtner, P. (Peter), Lindgren, C. M. (Cecilia M.), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Lorbeer, R. (Roberto), Lorentzon, M. (Mattias), Luben, R. (Robert), Lyssenko, V. (Valeriya), Mannisto, S. (Satu), Manunta, P. (Paolo), Leach, I. M. (Irene Mateo), McArdle, W. L. (Wendy L.), Mcknight, B. (Barbara), Mohlke, K. L. (Karen L.), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Montasser, M. E. (May E.), Morris, A. P. (Andrew P.), Mueller, G. (Gabriele), Musk, A. W. (Arthur W.), Narisu, N. (Narisu), Ong, K. K. (Ken K.), Oostra, B. A. (Ben A.), Osmond, C. (Clive), Palotie, A. (Aarno), Pankow, J. S. (James S.), Paternoster, L. (Lavinia), Penninx, B. W. (Brenda W.), Pichler, I. (Irene), Pilia, M. G. (Maria G.), Polasek, O. (Ozren), Pramstaller, P. P. (Peter P.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rayner, N. W. (Nigel W.), Ribel-Madsen, R. (Rasmus), Rice, T. K. (Treva K.), Richards, M. (Marcus), Ridker, P. M. (Paul M.), Rivadeneira, F. (Fernando), Ryan, K. A. (Kathy A.), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Scholtens, S. (Salome), Scott, R. A. (Robert A.), Sebert, S. (Sylvain), Southam, L. (Lorraine), Sparso, T. H. (Thomas Hempel), Steinthorsdottir, V. (Valgerdur), Stirrups, K. (Kathleen), Stolk, R. P. (Ronald P.), Strauch, K. (Konstantin), Stringham, H. M. (Heather M.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Toenjes, A. (Anke), Tsafantakis, E. (Emmanouil), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vandenput, L. (Liesbeth), Vartiainen, E. (Erkki), Venturini, C. (Cristina), Verweij, N. (Niek), Viikari, J. S. (Jorma S.), Vitart, V. (Veronique), Vohl, M.-C. (Marie-Claude), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Widen, E. (Elisabeth), Willemsen, G. (Gonneke), Wilsgaard, T. (Tom), Winkler, T. W. (Thomas W.), Wright, A. F. (Alan F.), Yerges-Armstrong, L. M. (Laura M.), Zhao, J. H. (Jing Hua), Zillikens, M. C. (M. Carola), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Cusi, D. (Daniele), Gansevoort, R. T. (Ron T.), Gieger, C. (Christian), Hansen, T. (Torben), Hicks, A. A. (Andrew A.), Hu, F. (Frank), Hveem, K. (Kristian), Jarvelin, M.-R. (Marjo-Riitta), Kajantie, E. (Eero), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Kuusisto, J. (Johanna), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Lehtimaeki, T. (Terho), Metspalu, A. (Andres), Njolstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A. J. (Albertine J.), Palmer, L. J. (Lyle J.), Pedersen, O. (Oluf), Perola, M. (Markus), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Puolijoki, H. (Hannu), Rauramaa, R. (Rainer), Rudan, I. (Igor), Salomaa, V. (Veikko), Schwarz, P. E. (Peter E. H.), Shudiner, A. R. (Alan R.), Smit, J. H. (Jan H.), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Timothy D.), Stefansson, K. (Kari), Stumvoll, M. (Michael), Tremblay, A. (Angelo), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Uusitupa, M. (Matti), Voelker, U. (Uwe), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Wilson, J. F. (James F.), Zeggini, E. (Eleftheria), Abecasis, G. R. (Goncalo R.), Boehnke, M. (Michael), Borecki, I. B. (Ingrid B.), Deloukas, P. (Panos), van Duijn, C. M. (Cornelia M.), Fox, C. (Caroline), Groop, L. C. (Leif C.), Heid, I. M. (Iris M.), Hunter, D. J. (David J.), Kaplan, R. C. (Robert C.), McCarthy, M. I. (Mark I.), North, K. E. (Kari E.), O'Connell, J. R. (Jeffrey R.), Schlessinger, D. (David), Thorsteinsdottir, U. (Unnur), Strachan, D. P. (David P.), Frayling, T. (Timothy), Hirschhorn, J. N. (Joel N.), Mueller-Nurasyid, M. (Martina), and Loos, R. J. (Ruth J. F.)

Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

Published
2016

49. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, Loos, RJF, Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, and Loos, RJF

Published
2016

50. Targeted therapy sensitivity and resistance in solid malignancies

Author

Jokinen, E. (Elina), Koivunen, J. (Jussi), and Turpeenniemi-Hujanen, T. (Taina)

Subjects
cancer stem cells, lääkeresistenssi, drug resistance, syövän kantasolut, molecular targeted therapy, karsinooma, molekulaarisesti kohdennettu hoito, carcinoma
Abstract

Cancer is a major global killer and a challenge for the healthcare worldwide. Earlier cancer has been treated with surgery, radiation, chemotherapy and hormonal therapy. Unfortunately the efficiency of these therapies has shown to be limited and this has raised an enthusiasm for development of new, targeted cancer therapies that are based on activated oncogenes. The challenge of the targeted therapies is therapy resistance, de novo, adaptive and acquired. This work investigated targeted therapy sensitivity and resistance in lung cancer, breast cancer, colorectal cancer, and melanoma cell lines. The results of this study indicate that in some non-small cell lung cancer cell lines, dual PI3K and MEK inhibition is a more efficacious treatment than inhibition of either solely. It was also showed that the maximal effect of the dual inhibition can be achieved with alternative dosing schedules that are potentially more tolerable in clinical use. Furthermore, by combining ABT-263, entinostat or dasatinib to the dual PI3K and MEK inhibition, the efficiency of the therapy can be increased. Bcl-xl downregulation is a major determinant of the apoptotic response to the triple inhibitor treatment. The current work showed that cancer stem cells can mediate resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with a targeted agent and a stem cell targeting drug might be needed for maximal therapeutic efficiency. This study also showed that Gö6976 acts as a potent inhibitor of mutant EGFR despite the presence of T790M, the most important mechanism of acquired resistance for EGFR tyrosine kinase inhibitors in lung cancer, both in vitro and in vivo. Tiivistelmä Syöpä on yksi johtavia kuolemanaiheuttajia ja tauti on maailmanlaajuinen haaste terveydenhuollolle. Perinteiset syöpähoidot käsittävät kirurgian, sädehoidon, kemoterapian ja hormonaalisen hoidon, mutta näiden rinnalle on noussut uusia, aktivoituneiden onkogeenien signaalien estoon perustuvia hoitoja. Tämä työ tutki kohdennettuja syöpähoitoja ja näihin hoitoihin liittyvää resistenssiä keuhko-, rinta- ja paksusuolen syövän sekä melanooman solulinjoissa. Tulokset osoittavat, että joissakin ei-pienisoluisen keuhkosyövän solulinjoissa yhdistetty PI3K- ja MEK-esto aiheuttaa tehokkaamman vasteen kuin kummankaan signaalireitin esto yksistään. Tässä työssä näytettiin myös, että maksimaalinen vaste yhdistetylle PI3K- ja MEK-estolle voidaan saavuttaa vaihtoehtoisilla annostelutavoilla, jotka ovat voisivat olla paremmin siedettyjä kliinisessä käytössä kuin kahden lääkkeen jatkuva annostelu. Tämä tutkimus osoitti lisäksi, että kaksoiseston tehokkuutta voidaan lisätä yhdistämällä hoitoon kolmas lääkeaine, ABT-263, entinostaatti tai dasatinibi. Bcl-xl proteiinilla on keskeinen rooli apoptoottisen vasteen määrittäjänä näille kolmen lääkkeen käsittelyille. Tämä työ osoitti, että syövän kantasolut voivat välittää resistenssiä kohdennetuille syöpähoidoille. Nämä solut noudattavat niin kutsuttua stokastista mallia, joten parhaan vasteen saaminen saattaa edellyttää että hoito kohdentuu sekä erilaistuneisiin että kantasolutyyppisiin syöpäsoluihin. Tässä tutkimuksessa osoitettin lisäksi, että Gö6976 toimii mutatoituneen EGFR:n estäjänä, huolimatta kehittyvää keuhkosyövissä resistenssiä välittävästä T90M mutaatiosta, sekä in vitro -että in vivo -malleissa.

Published
2014

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