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1. Overweight, obesity and hyperandrogenemia are associated with gestational diabetes mellitus:a follow‐up cohort study

Author: West, S. (Sammeli), Ollila, M. (Meri‐Maija), Franks, S. (Stephen), Piltonen, T. (Terhi), Jokelainen, J. (Jari), Nevalainen, J. (Jaana), Puukka, K. (Katri), Ruokonen, A. (Aimo), Järvelin, M. (Marjo‐Riitta), Auvinen, J. (Juha), Tapanainen, J. S. (Juha S.), and Morin‐Papunen, L. (Laure)
Subjects: endocrine system diseases, nutritional and metabolic diseases, Follow-up cohort study, Overweight, Hyperandrogenism, Gestational diabetes mellitus, female genital diseases and pregnancy complications, Polycystic ovary syndrome
Abstract: Introduction: The aim of the study was to determine the association of body mass index (BMI), self‐reported symptoms or diagnosis of polycystic ovary syndrome (PCOS), and hyperandrogenemia with the occurrence of gestational diabetes mellitus (GDM) through reproductive life. Material and methods: A cohort of women born in 1966 were investigated at ages 14, 31 and 46. Women with self‐reported PCOS symptoms (presence of both oligo‐amenorrhea and hirsutism) at age 31 or with formally diagnosed polycystic ovaries (PCO)/PCOS by age 46 formed the group of self‐reported PCOS (srPCOS, n = 222) and were compared with women without self‐reported PCOS symptoms or diagnosis (n = 1357). We investigated also the association of hyperandrogenism (hirsutism or biochemical hyperandrogenism) at age 31 with the occurrence of GDM throughout reproductive life. Results: Self‐reported PCOS alone was not a risk factor for GDM, but combined with overweight at age 31 (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.22‐4.86) or 46 (OR 3.04, 95% CI 1.58‐5.83) srPCOS was associated with GDM when compared with normal weight controls. The association disappeared when comparing overweight srPCOS women with overweight controls. However, hyperandrogenemia at age 31, but not hirsutism, was associated with GDM even after adjustment for BMI. Conclusions: The increased risk of GDM in women with srPCOS was mostly attributed to overweight or obesity. Importantly, normal weight women with srPCOS did not seem to be at increased risk for developing GDM. However, hyperandrogenemia was associated with GDM even after adjustment for BMI. These findings strengthen the importance of weight management in reproductive‐age women and suggest a noteworthy role of hyperandrogenemia in the pathophysiology of GDM.
Published: 2020

2. Current use of combined hormonal contraception is associated with glucose metabolism disorders in perimenopausal women

Author: Mosorin, M.-E. (Maria-Elina), Haverinen, A. (Annina), Ollila, M.-M. (Meri-Maija), Nordström, T. (Tanja), Jokelainen, J. (Jari), Keinänen-Kiukaanniemi, S. (Sirkka), Puukka, K. (Katri), Ruokonen, A. (Aimo), Auvinen, J. (Juha), Piltonen, T. (Terhi), Morin-Papunen, L. (Laure), and Tapanainen, J. S. (Juha S)
Abstract: Objective: The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial. Design: The study is a prospective longitudinal population-based cohort study. Methods: The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n = 153), progestin-only contraceptive (POC, n = 842), and non-hormonal contraceptive users (n = 884). Results: In the entire study population, current CHC use was significantly associated with prediabetes (OR: 2.0, 95% CI: 1.3–3.2) and type 2 diabetes (OR: 3.3, 95% CI: 1.1–9.7) compared to non-hormonal contraceptive use. After 5 years of use, the prediabetes risk increased 2.2-fold (95% CI: 1.3–3.7) and type 2 diabetes risk increased 4.5-fold (95% CI: 1.5–13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR: 1.9, 95% CI: 1.2–3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for BMI and socioeconomic status. Conclusions: CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.
Published: 2020

3. Gestational diabetes but not prepregnancy overweight predicts for cardiometabolic markers in offspring twenty years later

Author: Kaseva, N. (Nina), Vääräsmäki, M. (Marja), Sundvall, J. (Jouko), Matinolli, H.-M. (Hanna-Maria), Sipola, M. (Marika), Tikanmäki, M. (Marjaana), Heinonen, K. (Kati), Lano, A. (Aulikki), Wehkalampi, K. (Karoliina), Wolke, D. (Dieter), Ruokonen, A. (Aimo), Andersson, S. (Sture), Järvelin, M.-R. (Marjo-Riitta), Räikkönen, K. (Katri), Eriksson, J. G. (Johan G.), Kajantie, E. (Eero), Kaseva, N. (Nina), Vääräsmäki, M. (Marja), Sundvall, J. (Jouko), Matinolli, H.-M. (Hanna-Maria), Sipola, M. (Marika), Tikanmäki, M. (Marjaana), Heinonen, K. (Kati), Lano, A. (Aulikki), Wehkalampi, K. (Karoliina), Wolke, D. (Dieter), Ruokonen, A. (Aimo), Andersson, S. (Sture), Järvelin, M.-R. (Marjo-Riitta), Räikkönen, K. (Katri), Eriksson, J. G. (Johan G.), and Kajantie, E. (Eero)
Abstract: Context: Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m²] might adversely affect offspring cardiometabolic health. Objective: To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. Design: Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). Setting: Province of Uusimaa and Northern Finland. Participants: At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m² (controls; n = 556). Main Outcome Measures: We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. Results: Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, −12.4%; 95% CI, −20.2% to −3.9%; women, −33.2%; 95% CI, −46.3% to −16.8%), high-density lipoprotein (−6.6%; 95% CI, −10.9% to −2.2%), and apolipoprotein A1 (−4.5%; 95% CI, −7.5% to −1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. Conclusions: Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, wh
Published: 2019

4. Early determinants of metabolically healthy obesity in young adults:study of the Northern Finland Birth Cohort 1966

Author: Nedelec, R. (Rozenn), Jokelainen, J. (Jari), Miettunen, J. (Jouko), Ruokonen, A. (Aimo), Herzig, K.-H. (Karl-Heinz), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), and Sebert, S. (Sylvain)
Subjects: adiposity rebound, lifecourse, epidemiology, metabolically healthy obesity
Abstract: Background: A body of literature suggests a metabolically healthy phenotype in individuals with obesity. Despite important clinical implications, the early origins of metabolically healthy obesity (MHO) have received little attention. Objective: To assess the prevalence of MHO among the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years of age, examine its determinants in early life taking into account the sex specificity. Methods: We studied 3205 term-born cohort participants with data available for cardio-metabolic health outcomes at 31 years, and longitudinal height and weight data. After stratifying the population by sex, adult BMI and a strict definition of metabolic health (i.e., no risk factors meaning metabolic health), we obtained six groups. Repeated childhood height and weight measures were used to model early growth and early adiposity phenotypes. We employed marginal means adjusted for mother and child covariates including socio-economic status, birth weight and gestational-age, to compare differences between the groups. Results: The prevalence of adult MHO was 6% in men and 13.5% in women. Differences in adult metabolic status were linked to alterations in BMI and age at adiposity peak in infancy (p
Published: 2018

5. The association between low grade systemic inflammation and skin diseases:a cross-sectional survey in the Northern Finland Birth Cohort 1966

Author: Sinikumpu, S.-P. (Suvi-Päivikki), Huilaja, L. (Laura), Auvinen, J. (Juha), Jokelainen, J. (Jari), Puukka, K. (Katri), Ruokonen, A. (Aimo), Timonen, M. (Markku), and Tasanen, K. (Kaisa)
Subjects: fungal skin infection, atopic eczema, epidemiology, low grade inflammation, rosacea
Abstract: Low grade inflammation is associated with many noncommunicable diseases. The association between skin diseases in general and systemic inflammation has not previously been studied at the population level. A whole-body investigation on 1,930 adults belonging to Northern Finland Birth Cohort 1966 was performed and high sensitive C-reactive protein (CRP) level was measured as a marker of low grade inflammation in order to determine the association between low grade inflammation and skin diseases in an unselected adult population. After adjustment for confounding factors the following skin disorders were associated with low grade inflammation in multinomial logistic regression analysis: atopic eczema (OR 2.2, 95% CI 1.2–3.9), onychomycosis (OR 2.0, 1.2–3.2) and rosacea (OR 1.7, 1.1–2.5). After additionally adjusting for body mass index and systemic diseases, the risks for atopic eczema (OR 2.4, 1.3–4.6) and onychomycosis (OR 1.9, 1.1–3.1) remained statistically significant. In conclusion, low grade inflammation is present in several skin diseases.
Published: 2018

6. Weight gain and dyslipidemia in early adulthood associate with polycystic ovary syndrome:prospective cohort study

Author: Ollila, M. E. (Meri-Maija E.), Piltonen, T. (Terhi), Puukka, K. (Katri), Ruokonen, A. (Aimo), Järvelin, M.-R. (Marjo-Riitta), Tapanainen, J. S. (Juha S.), Franks, S. (Stephen), and Morin-Papunen, L. (Laure)
Subjects: nutritional and metabolic diseases
Abstract: Context: Obesity affects the majority of women with polycystic ovary syndrome (PCOS), but previous studies are inconsistent about the prevalence of obesity and the importance of weight gain in the development of the syndrome. Objective: Our objective was to explore the association between weight, weight gain, hyperandrogenism, and PCOS from adolescence to late adulthood. Design: The study includes a prospective Northern Finland Birth Cohort 1966 study including 5889 females born in 1966 and followed at the ages of 14, 31, and 46 years. Setting: The setting was the general community. Participants: Women presenting both oligo/amenorrhea (OA) and hirsutism (H) at age 31 (N = 125) or with formally diagnosed PCOS by age 46 (N = 181) were compared with women without PCOS symptoms or diagnosis (n = 1577). Interventions: None. Main Outcome Measures: Body mass index (BMI), weight change through life, waist circumference, Free Androgen Index, lipids, glucose, insulin, high-sensitivity C-reactive protein, homeostatic model assessment for insulin resistance, and PCOS. Results: Women with OA+H at age 31 or diagnosis of PCOS by age 46 had the highest BMI at all ages compared with the controls. Increase of BMI between ages 14 and 31, but not between 31 and 46, was greater in women with isolated OA (P = 0.006), OA+H (P = 0.001), and diagnosis of PCOS (P = 0.001) compared with controls. In the multivariate analysis, PCOS was significantly associated with BMI at all ages (BMI at age 31: odds ratio [OR] = 1.05 [95% confidence interval (CI), 1.00–1.10], Free Androgen Index (OR = 1.08 [95% CI, 1.03–1.14]), serum levels of insulin (OR = 1.05 [95% CI, 1.00–1.09]), and triglycerides (OR = 1.48 [95% CI, 1.08–2.03]). Conclusions: Symptoms or diagnosis of PCOS are associated with dyslipidemia, hyperandrogenemia, and significantly increased weight gain, especially in early adulthood. This observation is important because it may identify a sensitive time period when weight gain plays a crucial role in the emergence of PCOS and when preventive actions against metabolic and cardiovascular diseases should be implemented.
Published: 2016

7. Fitness, fatness, physical activity, and autonomic function in midlife

Author: Kiviniemi, A. M. (Antti M.), Perkiömäki, N. (Nelli), Auvinen, J. (Juha), Niemelä, M. (Maisa), Tammelin, T. (Tuija), Puukka, K. (Katri), Ruokonen, A. (Aimo), Keinänen-Kiukaanniemi, S. (Sirkka), Tulppo, M. P. (Mikko P.), Järvelin, M.-R. (Marjo-Riitta), Jämsä, T. (Timo), Huikuri, H. V. (Heikki V.), Korpelainen, R. (Raija), Kiviniemi, A. M. (Antti M.), Perkiömäki, N. (Nelli), Auvinen, J. (Juha), Niemelä, M. (Maisa), Tammelin, T. (Tuija), Puukka, K. (Katri), Ruokonen, A. (Aimo), Keinänen-Kiukaanniemi, S. (Sirkka), Tulppo, M. P. (Mikko P.), Järvelin, M.-R. (Marjo-Riitta), Jämsä, T. (Timo), Huikuri, H. V. (Heikki V.), and Korpelainen, R. (Raija)
Abstract: Purpose: Although low cardiorespiratory fitness (CRF), physical inactivity, and obesity are associated with impaired autonomic function, they are also extensively interrelated. The present study aimed to assess the extent to which they contribute to autonomic function independently of each other. Methods: At the age of 46 yr, 1383 men and 1761 women without cardiorespiratory diseases and diabetes underwent assessments of vagally mediated heart rate (HR) variability (root mean square of successive differences in R-R interval (rMMSD)), peak HR during a submaximal step test (CRF), and 60-s HR recovery (HRR). Moderate-to-vigorous physical activity (MVPA; ≥3.5 METs, 2 wk) was measured by wrist-worn accelerometer and body fat percentage (Fat%) by bioimpedance Results: In men, CRF and Fat% were significantly associated with higher rMSSD (standardized β = 0.31 and -0.16) and HRR (β = 0.19 and -0.18), whereas higher MVPA was linked with higher HRR (β = 0.13) when including CRF, MVPA, and Fat% in the initial regression. After adjustments for other lifestyle and cardiometabolic factors, CRF remained significantly associated with rMMSD (β = 0.24) and HRR (β = 0.14), as did MVPA with HRR (β = 0.11). In women, CRF was associated with rMSSD (β = 0.23) and HRR (β = 0.15), and MVPA (β = 0.17) and Fat% (β = -0.07) with HRR, when CRF, MVPA, and Fat% were adjusted for each other. After further adjustments, CRF remained a significant determinant of rMSSD (β = 0.20) and HRR (β = 0.13), as did MVPA with HRR (β = 0.15). The final models explained 23% and 21% of variation in rMSSD and HRR in men, and 10% and 12% in women, respectively. Conclusions: CRF was a more important determinant of cardiac autonomic function than MVPA and body fat. Furthermore, MVPA but not body fat was independently associated with cardiac autonomic function in both men and women.
Published: 2017

8. Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

Author: Pinola, P. (Pekka), Puukka, K. (Katri), Piltonen, T. T. (Terhi T.), Puurunen, J. (Johanna), Vanky, E. (Eszter), Sundström-Poromaa, I. (Inger), Stener-Victorin, E. (Elisabet), Lindén Hirschberg, A. (Angelica), Ravn, P. (Pernille), Skovsager Andersen, M. (Marianne), Glintborg, D. (Dorte), Roar Mellembakken, J. (Jan), Ruokonen, A. (Aimo), Tapanainen, J. S. (Juha S.), Morin-Papunen, L. C. (Laure C.), Pinola, P. (Pekka), Puukka, K. (Katri), Piltonen, T. T. (Terhi T.), Puurunen, J. (Johanna), Vanky, E. (Eszter), Sundström-Poromaa, I. (Inger), Stener-Victorin, E. (Elisabet), Lindén Hirschberg, A. (Angelica), Ravn, P. (Pernille), Skovsager Andersen, M. (Marianne), Glintborg, D. (Dorte), Roar Mellembakken, J. (Jan), Ruokonen, A. (Aimo), Tapanainen, J. S. (Juha S.), and Morin-Papunen, L. C. (Laure C.)
Abstract: Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30–39, and >39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
Published: 2017

9. Psychological distress is more prevalent in fertile age and premenopausal women with PCOS symptoms:15-year follow-up

Author: Karjula, S. (Salla), Morin-Papunen, L. (Laure), Auvinen, J. (Juha), Ruokonen, A. (Aimo), Puukka, K. (Katri), Franks, S. (Stephen), Järvelin, M.-R. (Marjo-Riitta), Tapanainen, J. S. (Juha S.), Jokelainen, J. (Jari), Miettunen, J. (Jouko), Piltonen, T. T. (Terhi T.), Karjula, S. (Salla), Morin-Papunen, L. (Laure), Auvinen, J. (Juha), Ruokonen, A. (Aimo), Puukka, K. (Katri), Franks, S. (Stephen), Järvelin, M.-R. (Marjo-Riitta), Tapanainen, J. S. (Juha S.), Jokelainen, J. (Jari), Miettunen, J. (Jouko), and Piltonen, T. T. (Terhi T.)
Abstract: Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression.
Published: 2017

10. Abnormal skin in toe webs is a marker for abnormal glucose metabolism:a cross-sectional survey among 1,849 adults in Finland

Author: Sinikumpu, S.-P. (Suvi-Päivikki), Auvinen, J. (Juha), Jokelainen, J. (Jari), Huilaja, L. (Laura), Puukka, K. (Katri), Ruokonen, A. (Aimo), Keinänen-Kiukaanniemi, S. (Sirkka), Tasanen, K. (Kaisa), Timonen, M. (Markku), Sinikumpu, S.-P. (Suvi-Päivikki), Auvinen, J. (Juha), Jokelainen, J. (Jari), Huilaja, L. (Laura), Puukka, K. (Katri), Ruokonen, A. (Aimo), Keinänen-Kiukaanniemi, S. (Sirkka), Tasanen, K. (Kaisa), and Timonen, M. (Markku)
Abstract: Diabetes is undiagnosed disease and easy screening tools for it are warranted. Because foot complications are usual in diabetes, we aimed to test hypothesis that skin abnormalities are found already from patients who are not aware of having diabetes, by studying the possible association between unhealthy toe web skin and abnormal glucose metabolism. 1,849 cases without previously diagnosed diabetes participated to the 46-year follow-up study of the Northern Finland Birth Cohort. A skin investigation was performed for all, and abnormal skin findings in toe web spaces were taken as explanatory variables. Abnormal glucose tolerance was the main outcome and it was tested with an oral glucose tolerance test (OGTT), glycosylated haemoglobin fraction (HbA1c) Values are numbers (percentages) of sub and fasting blood glucose. The participants who had any abnormal skin findings in toe webs were associated with 2.5-fold (OR 2.5, 95% CI 1.3–4.9) and 6-fold (OR 6.2, 1.4–27.6) increased risk of having previously undiagnosed diabetes detected by a 2-hour OGTT and HbA1c, respectively. The predictive power of toe web findings was comparable with FINDRISC score. Abnormal skin findings in the toe webs show increased risk of occult diabetes, and may, thus serve as an additional sign of undiagnosed diabetes.
Published: 2017

11. Association between birth characteristics and cardiovascular autonomic function at mid-life

Author: Perkiömäki, N. (Nelli), Auvinen, J. (Juha), Tulppo, M. P. (Mikko P.), Hautala, A. J. (Arto J.), Perkiömäki, J. (Juha), Karhunen, V. (Ville), Keinänen-Kiukaanniemi, S. (Sirkka), Puukka, K. (Katri), Ruokonen, A. (Aimo), Järvelin, M.-R. (Marjo-Riitta), Huikuri, H. V. (Heikki V.), Kiviniemi, A. M. (Antti M.), Perkiömäki, N. (Nelli), Auvinen, J. (Juha), Tulppo, M. P. (Mikko P.), Hautala, A. J. (Arto J.), Perkiömäki, J. (Juha), Karhunen, V. (Ville), Keinänen-Kiukaanniemi, S. (Sirkka), Puukka, K. (Katri), Ruokonen, A. (Aimo), Järvelin, M.-R. (Marjo-Riitta), Huikuri, H. V. (Heikki V.), and Kiviniemi, A. M. (Antti M.)
Abstract: Background: Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. Methods: At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965–1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. Results: In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500–3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). Conclusions: In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not
Published: 2016

12. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

Author: Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), Chasman., D.I. (Daniel I.), Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), and Chasman., D.I. (Daniel I.)
Abstract: Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.
Published: 2015
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13. Interactive two-step training and management strategy for improvement of the quality of point-of-care testing by nurses:implementation of the strategy in blood glucose measurement

Author: Ruokonen, A. (Aimo), Liikanen, E. (Eeva), Lehto, L. (Liisa), Ruokonen, A. (Aimo), Liikanen, E. (Eeva), and Lehto, L. (Liisa)
Abstract: Point-of-care testing (POCT) is defined as laboratory tests performed outside the traditional clinical laboratory close to the patient at the time and place where care is received, such as hospitals and healthcare centers. The main reason for the use of POCT is that they provide rapid results and enable prompt interventions, with hopefully improved patient outcomes. All phases of laboratory procedure are included in POCT offering many opportunities for errors, which can influence on patients’ treatment. The measurements are more often performed by nurses than by laboratory professionals. These nurses have different kinds of professional backgrounds, e.g. public health nurses, registered and practical nurses, with minimal or no knowledge of laboratory procedures. The aim of the study was to develop a two-step training and management strategy for nurses to do POCT in hospital and primary healthcare center. In accordance with the strategy, with reasonable investment of laboratory resources, designated contact nurses were first trained in POCT by laboratory professionals, after which the contact nurses trained other nurses in POCT their respective units. Blood glucose, the most common point-of-care (POC) test, was chosen as an example to investigate the influence of training on the quality of the test performed by nurses. The quality of blood glucose measurements was studied by analyzing the control results obtained by nurses and biomedical laboratory scientists (BLSs). The study participants included nurses who were either untrained or trained to do POCT by using the developed interactive two-step training strategy. In conclusion, the nurses trained by using interactive two-step strategy achieved near-similar quality of blood glucose measurements as BLSs. The good quality of glucose measurements, once achieved by training, was also sustained in the long-term., Tiivistelmä Määritelmän mukaan vieritutkimuksiksi kutsutaan laboratoriotutkimuksia, joita tehdään perinteisen laboratorion ulkopuolella, tarvittaessa lähellä potilasta sairaalassa ja perusterveydenhuollon alueella. Pääasiassa vieritutkimuksia tehdään silloin kun tulos halutaan saada nopeasti ennen hoitopäätöstä tai tulevaa toimenpidettä. Vieritutkimusten tekeminen sisältää kaikki laboratoriotyön vaiheet ja jokaisessa vaiheessa on mahdollisuus tehdä virheitä, jotka voivat vaikuttaa potilaiden hoitoon. Laboratorioammattilaisten sijaan määrityksiä tekevät yhä useammin hoitajat sairaalan eri yksiköissä ja perusterveydenhuollon alueella. Näillä hoitajilla on erilainen ammatillinen peruskoulutus, kuten perushoitajan tai sairaanhoitajan koulutus, ja heillä on vähän tai ei ollenkaan tietoa laboratoriomenetelmistä. Tämän tutkimuksen tarkoituksena oli kehittää hoitajien vieritutkimustoimintaan koulutus- ja hallintomalli, joka toimisi sekä sairaalassa että terveyskeskuksessa. Strategian perusteena oli käyttää suhteellisen vähän laboratorioresursseja ja päästä silti hyvään laadulliseen lopputulokseen. Strategiaksi valittiin kaksiportainen, vuorovaikutteinen koulutusmalli, jossa laboratorioammattilaiset kouluttivat sairaalan ja perusterveydenhuollon yksiköissä ns. yhdyshenkilöt, jotka puolestaan kouluttivat edelleen oman yksikkönsä muut hoitajat tekemään vieritutkimuksia. Veren glukoosimääritys, joka on yleisin vieritutkimus, valittiin esimerkkitutkimukseksi tutkittaessa koulutuksen vaikutusta hoitajien tekemien vieritutkimusten laatuun. Veren glukoosimääritysten laatutasoa tutkittiin analysoimalla hoitajien ja laboratoriohoitajien tekemien kontrollinäytteiden tuloksia. Tutkimukseen osallistui hoitajia, jotka oli koulutettu kehitetyllä vuorovaikutteisella kaksiportaisella koulutusstrategialla vieritutkimusten tekemiseen, sekä hoitajia, jotka eivät olleet saaneet vastaavaa koulutusta. Koulutusmallin avulla hoitajien suorittamien vieritutkimusten laatu parani ja he saavuttivat läh
Published: 2014

14. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Author: Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Prokopenko, I. (Inga), Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), and Prokopenko, I. (Inga)
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05).
Published: 2013
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15. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in s

Author: Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), Perry, J.R.B. (John), Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), and Perry, J.R.B. (John)
Abstract: Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG, PRMT6, GCKR, ZBTB10, JMJD1C, SLCO1B1, NR2F2, ZNF652, TDGF3, LHCGR, BAIAP2L1, and UGT2B15. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
Published: 2012
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16. Genetic variants influencing circulating lipid levels and risk of coronary artery disease

Author: Waterworth, D. (Dawn), Ricketts, S.L. (Sally), Song, K. (Kijoung), Chen, L. (Leslie), Zhao, J.H. (Jing Hua), Ripatti, S. (Samuli), Aulchenko, Y.S. (Yurii), Zhang, W. (Weihua), Yuan, X. (Xin), Lim, N. (Noha), Luan, J., Ashford, S. (Sofie), Wheeler, E. (Eleanor), Young, E.H. (Elizabeth), Hadley, D. (David), Thompson, J.R. (John), Braund, P.S. (Peter), Johnson, T. (Toby), Struchalin, M.V. (Maksim), Surakka, I. (Ida), Luben, R.N. (Robert), Khaw, K-T. (Kay-Tee), Rodwell, S.A. (Sheila), Loos, R.J.F. (Ruth), Boekholdt, S.M. (Matthijs), Inouye, M. (Michael), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Schlessinger, D., Sanna, S. (Serena), Scuteri, A. (Angelo), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Roberts, R. (Robert), Stewart, A. (Alison), Kesaniemi, Y.A. (Antero), Mahley, R. (Robert), Grundy, S.M. (Scott), McArdle, W.L. (Wendy), Cardon, L. (Lon), Waeber, G. (Gérard), Vollenweider, P. (Peter), Chambers, J.C. (John), Boehnke, M. (Michael), Abecasis, G.R. (Gonçalo), Salomaa, V. (Veikko), Järvelin, M.R., Ruokonen, A. (Aimo), Barroso, I.E. (Inês), Epstein, S.E. (Stephen), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Witteman, J.C.M. (Jacqueline), Hall, A.S. (Alistair), Samani, N.J. (Nilesh), Strachan, D.P. (David), Barter, P. (Phil), Tikka-Kleemola, P. (Päivi), Kooner, J.S. (Jaspal), Peltonen, L. (Leena Johanna), Wareham, N.J. (Nick), McPherson, R. (Ruth), Mooser, V. (Vincent), Sandhu, M.S. (Manjinder), Waterworth, D. (Dawn), Ricketts, S.L. (Sally), Song, K. (Kijoung), Chen, L. (Leslie), Zhao, J.H. (Jing Hua), Ripatti, S. (Samuli), Aulchenko, Y.S. (Yurii), Zhang, W. (Weihua), Yuan, X. (Xin), Lim, N. (Noha), Luan, J., Ashford, S. (Sofie), Wheeler, E. (Eleanor), Young, E.H. (Elizabeth), Hadley, D. (David), Thompson, J.R. (John), Braund, P.S. (Peter), Johnson, T. (Toby), Struchalin, M.V. (Maksim), Surakka, I. (Ida), Luben, R.N. (Robert), Khaw, K-T. (Kay-Tee), Rodwell, S.A. (Sheila), Loos, R.J.F. (Ruth), Boekholdt, S.M. (Matthijs), Inouye, M. (Michael), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Schlessinger, D., Sanna, S. (Serena), Scuteri, A. (Angelo), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Roberts, R. (Robert), Stewart, A. (Alison), Kesaniemi, Y.A. (Antero), Mahley, R. (Robert), Grundy, S.M. (Scott), McArdle, W.L. (Wendy), Cardon, L. (Lon), Waeber, G. (Gérard), Vollenweider, P. (Peter), Chambers, J.C. (John), Boehnke, M. (Michael), Abecasis, G.R. (Gonçalo), Salomaa, V. (Veikko), Järvelin, M.R., Ruokonen, A. (Aimo), Barroso, I.E. (Inês), Epstein, S.E. (Stephen), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), Witteman, J.C.M. (Jacqueline), Hall, A.S. (Alistair), Samani, N.J. (Nilesh), Strachan, D.P. (David), Barter, P. (Phil), Tikka-Kleemola, P. (Päivi), Kooner, J.S. (Jaspal), Peltonen, L. (Leena Johanna), Wareham, N.J. (Nick), McPherson, R. (Ruth), Mooser, V. (Vincent), and Sandhu, M.S. (Manjinder)
Abstract: OBJECTIVE-: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS
Published: 2010
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17. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Author: Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), Barroso, I.E. (Inês), Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), and Barroso, I.E. (Inês)
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Published: 2010
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18. Biological, clinical and population relevance of 95 loci for blood lipids

Author: Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Teslovich, T.M. (Tanya), Musunuru, K. (Kiran), Smith, A.V. (Albert Vernon), Edmondson, A.C. (Andrew), Stylianou, I.M. (Ioannis), Koseki, M. (Masahiro), Pirruccello, J.P. (James), Ripatti, S. (Samuli), Chasman, D.I. (Daniel), Willer, C.J. (Cristen), Johansen, C.T. (Christopher), Fouchier, S.W. (Sigrid), Isaacs, A.J. (Aaron), Peloso, G.M. (Gina), Barbalic, M. (maja), Ricketts, S.L. (Sally), Bis, J.C. (Joshua), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), Feitosa, M.F. (Mary Furlan), Chambers, J. (John), Orho-Melander, M. (Marju), Melander, O. (Olle), Johnson, T. (Toby), Li, X. (Xiaohui), Guo, X. (Xiuqing), Shin Cho, Y. (Yoon), Jin Go, M. (Min), Jin Kim, Y. (Young), Lee, J.Y. (Jong Young), Park, T. (Taesung), Kim, Y-J. (Yong-Jin), Sim, X. (Xueling), Twee-Hee Ong, R. (Rick), Croteau-Chonka, D.C. (Damien), Lange, L.A. (Leslie), Song, K. (Kijoung), Zhao, J.H. (Jing Hua), Yuan, X. (Xin), Luan, J., Lamina, C. (Claudia), Ziegler, A. (Andreas), Zhang, W. (Weibo), Zee, R.Y.L. (Robert), Wright, A.F. (Alan), Witteman, J.C.M. (Jacqueline), Wilson, J.F. (James), Willemsen, G.A.H.M. (Gonneke), Wichmann, H.E. (Heinz Erich), Whitfield, J. (John), Waterworth, D. (Dawn), Wareham, N.J. (Nick), Waeber, G. (Gérard), Vollenweider, P. (Peter), Voight, B.F. (Benjamin), Vitart, V. (Veronique), Uitterlinden, A.G. (André), Uda, M. (Manuela), Tuomilehto, J. (Jaakko), Thompson, J.R. (John), Tanaka, T. (Toshiko), Surakka, I. (Ida), Stringham, H.M. (Heather), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Smit, J.H. (Johannes), Sinisalo, J. (Juha), Silander, K. (Kaisa), Sijbrands, E.J.G. (Eric), Scuteri, A. (Angelo), Scott, J. (James), Schlessinger, D. (David), Sanna, S. (Serena), Salomaa, V. (Veikko), Saharinen, J. (Juha), Sabatti, C. (Chiara), Ruokonen, A. (Aimo), Rudan, I. (Igor), Rose, L.M. (Lynda), Roberts, R. (Robert), Rieder, M. (Mark), Psaty, B.M. (Bruce), Pramstaller, P.P. (Peter Paul), Pichler, I. (Irene), Perola, M. (Markus), Penninx, B.W.J.H. (Brenda), Pedersen, N.L. (Nancy), Pattaro, C. (Cristian), Parker, A.N. (Alex), Pare, G. (Guillaume), Oostra, B.A. (Ben), Nieminen, M.S. (Markku), Nickerson, D.A. (Deborah), Montgomery, G.W. (Grant), Meitinger, T. (Thomas), McPherson, R. (Ruth), McCarthy, M.I. (Mark), McArdle, W.L. (Wendy), Masson, D. (David), Martin, N.G. (Nicholas), Marroni, F. (Fabio), Mangino, M. (Massimo), Magnusson, P.K. (Patrik), Lucas, G. (Gavin), Luben, R.N. (Robert), Loos, R.J.F. (Ruth), Lokki, M.L., Lettre, G. (Guillaume), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lakatta, E. (Edward), Laaksonen, R. (Reijo), Kyvik, K.O. (Kirsten Ohm), Kronenberg, F. (Florian), König, I.R. (Inke), Khaw, K-T. (Kay-Tee), Kaprio, J. (Jaakko), Kaplan, R.C. (Robert), Johansson, A. (Åsa), Jarvelin, M.-R. (Marjo-Riitta), Cecile, A. (A.), Ingelsson, E. (Erik), Igl, W. (Wilmar), Hovingh, G.K. (Kees), Hottenga, J.J. (Jouke Jan), Hofman, A. (Albert), Hicks, A.A. (Andrew), Hengstenberg, C. (Christian), Heid, I.M. (Iris), Hayward, C. (Caroline), Havulinna, A.S. (Aki), Hastie, N. (Nick), Harris, T.B. (Tamara), Haritunians, T. (Talin), Hall, A.S. (Alistair), Gyllensten, U. (Ulf), Guiducci, C. (Candace), Groop, L. (Leif), Gonzalez, E. (Elena), Gieger, C. (Christian), Freimer, N.B. (Nelson), Ferrucci, L. (Luigi), Erdmann, J. (Jeanette), Elliott, P. (Paul), Ejebe, K.G. (Kenechi), Döring, A. (Angela), Dominiczak, A. (Anna), Demissie, S. (Serkalem), Deloukas, P. (Panagiotis), Geus, E.J.C. (Eco) de, Faire, U. (Ulf) de, Crawford, G. (Gabe), Collins, F.S. (Francis), Chen, C. (Chao), Caulfield, M. (Mark), Campbell, H. (Harry), Burtt, N.P. (Noël), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Boekholdt, S.M. (Matthijs), Bergman, R.N. (Richard), Barroso, I.E. (Inês), Bandinelli, S. (Stefania), Ballantyne, C. (Christie), Assimes, T.L. (Themistocles), Quertermous, T. (Thomas), Altshuler, D. (David), Seielstad, M. (Mark), Wong, T.Y. (Tien Yin), Tai, E.S. (Shyong), Feranil, A.B. (Alan), Kuzawa, C.W. (Christopher), Adair, L.S. (Linda), Taylor, H.A. (Herman), Borecki, I.B. (Ingrid), Gabriel, S.B. (Stacey), Holm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Gudnason, V. (Vilmundur), Krauss, R.M. (Ronald), Mohlke, K.L. (Karen), Ordovas, J.M. (Jose), Munroe, P. (Patricia), Kooner, J.S. (Jaspal), Tall, A.R. (Alan), Hegele, R.A. (Robert), Kastelein, J.J.P. (John), Schadt, E.E. (Eric), Rotter, J.I. (Jerome), Boerwinkle, E.A. (Eric), Strachan, D.P. (David), Mooser, V. (Vincent), Zwart, J-A. (John-Anker), Reilly, M.P. (Muredach), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Cupples, L.A. (Adrienne), Sandhu, M.S. (Manjinder), Ridker, P.M. (Paul), Rader, D.J. (Daniel), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), Kathiresan, S. (Sekar), and O'Donnell, C.J. (Christopher)
Abstract: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<-10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Published: 2010
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19. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), Weedon, M.N. (Michael), Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), and Weedon, M.N. (Michael)
Abstract: Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation.
Published: 2010
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20. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

Author: Aulchenko, Y.S. (Yurii), Ripatti, S. (Samuli), Lindqvist, I. (Ida), Boomsma, D.I. (Dorret), Heid, I.M. (Iris), Pramstaller, P.P. (Peter Paul), Penninx, B.W.J.H. (Brenda), Janssens, A.C.J.W. (Cécile), Wilson, J.F. (James), Spector, T.D. (Timothy), Martin, N.G. (Nicholas), Pedersen, N.L. (Nancy), Kyvik, K.O. (Kirsten Ohm), Kaprio, J. (Jaakko), Hofman, A. (Albert), Freimer, N.B. (Nelson), Jarvelin, M.-R. (Marjo-Riitta), Gyllensten, U. (Ulf), Campbell, H. (Harry), Rudan, I. (Igor), Johansson, A. (Åsa), Marroni, F. (Fabio), Hayward, C. (Caroline), Vitart, V. (Veronique), Jonasson, I. (Inger), Pattaro, C. (Cristian), Wright, A. (Alan), Hastie, N. (Nick), Pichler, I. (Irene), Hicks, A.A. (Andrew), Falchi, M. (Mario), Willemsen, G.A.H.M. (Gonneke), Hottenga, J.J. (Jouke Jan), Geus, E.J.C. (Eco) de, Montgomery, G.W. (Grant), Whitfield, J. (John), Magnusson, P. (Patrik), Saharinen, J. (Juha), Perola, M. (Markus), Silander, K. (Kaisa), Isaacs, A.J. (Aaron), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Oostra, B.A. (Ben), Elliott, P. (Paul), Ruokonen, A. (Aimo), Sabatti, C. (Chiara), Gieger, C. (Christian), Meitinger, T. (Thomas), Kronenberg, F. (Florian), Döring, A. (Angela), Wichmann, H.E. (Erich), Smit, J.H. (Johannes), McCarthy, M.I. (Mark), Tikka-Kleemola, P. (Päivi), Peltonen, L. (Leena Johanna), Aulchenko, Y.S. (Yurii), Ripatti, S. (Samuli), Lindqvist, I. (Ida), Boomsma, D.I. (Dorret), Heid, I.M. (Iris), Pramstaller, P.P. (Peter Paul), Penninx, B.W.J.H. (Brenda), Janssens, A.C.J.W. (Cécile), Wilson, J.F. (James), Spector, T.D. (Timothy), Martin, N.G. (Nicholas), Pedersen, N.L. (Nancy), Kyvik, K.O. (Kirsten Ohm), Kaprio, J. (Jaakko), Hofman, A. (Albert), Freimer, N.B. (Nelson), Jarvelin, M.-R. (Marjo-Riitta), Gyllensten, U. (Ulf), Campbell, H. (Harry), Rudan, I. (Igor), Johansson, A. (Åsa), Marroni, F. (Fabio), Hayward, C. (Caroline), Vitart, V. (Veronique), Jonasson, I. (Inger), Pattaro, C. (Cristian), Wright, A. (Alan), Hastie, N. (Nick), Pichler, I. (Irene), Hicks, A.A. (Andrew), Falchi, M. (Mario), Willemsen, G.A.H.M. (Gonneke), Hottenga, J.J. (Jouke Jan), Geus, E.J.C. (Eco) de, Montgomery, G.W. (Grant), Whitfield, J. (John), Magnusson, P. (Patrik), Saharinen, J. (Juha), Perola, M. (Markus), Silander, K. (Kaisa), Isaacs, A.J. (Aaron), Sijbrands, E.J.G. (Eric), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Oostra, B.A. (Ben), Elliott, P. (Paul), Ruokonen, A. (Aimo), Sabatti, C. (Chiara), Gieger, C. (Christian), Meitinger, T. (Thomas), Kronenberg, F. (Florian), Döring, A. (Angela), Wichmann, H.E. (Erich), Smit, J.H. (Johannes), McCarthy, M.I. (Mark), Tikka-Kleemola, P. (Päivi), and Peltonen, L. (Leena Johanna)
Abstract: Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 × 10-8), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 × 10-11; LDL, P = 2.6 × 10-10), TMEM57 (TC, P = 5.4 × 10-10), CTCF-PRMT8 region (HDL, P = 8.3 × 10-16), DNAH11 (LDL, P = 6.1 × 10-9), FADS3-FADS2 (TC, P = 1.5 × 10-10; LDL, P = 4.4 × 10-13) and MADD-FOLH1 region (HDL, P = 6 × 10-11). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
Published: 2009
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21. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Author: Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), McCarthy, M.I. (Mark), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), and McCarthy, M.I. (Mark)
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102-11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10-8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human
Published: 2009
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22. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Author: Willer, C.J. (Cristen), Speliotes, E.K. (Elizabeth), Loos, R.J.F. (Ruth), Li, S. (Shengxu), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Berndt, S.I. (Sonja), Elliott, A.L. (Amanda), Jackson, A.U. (Anne), Lamina, C. (Claudia), Lettre, G. (Guillaume), Lim, N. (Noha), Lyon, H.N. (Helen), McCarroll, S.A. (Steven), Papadakis, K. (Konstantinos), Qi, L. (Lu), Randall, J.C. (Joshua), Roccasecca, R.M., Sanna, S. (Serena), Scheet, P. (Paul), Weedon, M.N. (Michael), Wheeler, E. (Eleanor), Zhao, J.H. (Jing Hua), Jacobs, L.C. (Leonie), Prokopenko, I. (Inga), Soranzo, N. (Nicole), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Almgren, P. (Peter), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bingham, S. (Sheila), Bonnycastle, L.L. (Lori), Brown, M.J. (Morris), Burtt, N.P. (Noël), Chines, P.S. (Peter), Coin, L. (Lachlan), Collins, F.S. (Francis), Connell, J. (John), Cooper, C. (Charles), Smith, A.V. (Davey), Dennison, E.M. (Elaine), Deodhar, P. (Parimal), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Evans, D.M. (David), Gianniny, L. (Lauren), Gieger, C. (Christian), Gillson, C.J. (Christopher), Guiducci, C. (Candace), Hackett, R. (Rachel), Hadley, D. (David), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hebebrand, J. (Johannes), Hofman, A. (Albert), Isomaa, B. (Bo), Johnson, T. (Toby), Jousilahti, P. (Pekka), Jovanovic, Z. (Zorica), Khaw, K-T. (Kay-Tee), Kraft, P. (Peter), Kuokkanen, M. (Mikko), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakatta, E. (Edward), Luan, J., Luben, R.N. (Robert), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Mulas, A. (Antonella), Munroe, P. (Patricia), Narisu, N. (Narisu), Ness, A.R. (Andrew), Northstone, K. (Kate), O'Rahilly, S. (Stephen), Purmann, C. (Carolin), Rees, M.G. (Matthew), Ridderstråle, M. (Martin), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Sandhu, M.S. (Manjinder), Saramies, J. (Jouko), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Sims, M.A. (Matthew), Song, K. (Kijoung), Stephens, J. (Jonathan), Stevens, S. (Suzanne), Stringham, H.M. (Heather), Tung, Y.C.L. (Loraine), Valle, T.T. (Timo), Tikka-Kleemola, P. (Päivi), Vimaleswaran, K.S. (Karani), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Watanabe, R.M. (Richard), Waterworth, D. (Dawn), Watkins, N. (Nicholas), Witteman, J.C.M. (Jacqueline), Zeggini, E. (Eleftheria), Zhai, G. (Guangju), Zillikens, M.C. (Carola), Altshuler, D. (David), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Farooqi, I.S. (Sadaf), Ferrucci, L. (Luigi), Guralnik, J.M. (Jack), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Laakso, M. (Markku), Mooser, V. (Vincent), Ong, K.K. (Ken), Ouwehand, W.H. (Willem), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Wareham, N.J. (Nick), Frayling, T.M. (Timothy), Groop, L. (Leif), Hayes, R.B. (Richard), Hunter, D. (David), Mohlke, K.L. (Karen), Peltonen, L. (Leena Johanna), Schlessinger, D. (David), Strachan, D.P. (David), Wichmann, H.E. (Erich), McCarthy, M.I. (Mark), Boehnke, M. (Michael), Barroso, I.E. (Inês), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Willer, C.J. (Cristen), Speliotes, E.K. (Elizabeth), Loos, R.J.F. (Ruth), Li, S. (Shengxu), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Berndt, S.I. (Sonja), Elliott, A.L. (Amanda), Jackson, A.U. (Anne), Lamina, C. (Claudia), Lettre, G. (Guillaume), Lim, N. (Noha), Lyon, H.N. (Helen), McCarroll, S.A. (Steven), Papadakis, K. (Konstantinos), Qi, L. (Lu), Randall, J.C. (Joshua), Roccasecca, R.M., Sanna, S. (Serena), Scheet, P. (Paul), Weedon, M.N. (Michael), Wheeler, E. (Eleanor), Zhao, J.H. (Jing Hua), Jacobs, L.C. (Leonie), Prokopenko, I. (Inga), Soranzo, N. (Nicole), Tanaka, T. (Toshiko), Timpson, N.J. (Nicholas), Almgren, P. (Peter), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bingham, S. (Sheila), Bonnycastle, L.L. (Lori), Brown, M.J. (Morris), Burtt, N.P. (Noël), Chines, P.S. (Peter), Coin, L. (Lachlan), Collins, F.S. (Francis), Connell, J. (John), Cooper, C. (Charles), Smith, A.V. (Davey), Dennison, E.M. (Elaine), Deodhar, P. (Parimal), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Evans, D.M. (David), Gianniny, L. (Lauren), Gieger, C. (Christian), Gillson, C.J. (Christopher), Guiducci, C. (Candace), Hackett, R. (Rachel), Hadley, D. (David), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hebebrand, J. (Johannes), Hofman, A. (Albert), Isomaa, B. (Bo), Johnson, T. (Toby), Jousilahti, P. (Pekka), Jovanovic, Z. (Zorica), Khaw, K-T. (Kay-Tee), Kraft, P. (Peter), Kuokkanen, M. (Mikko), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakatta, E. (Edward), Luan, J., Luben, R.N. (Robert), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Mulas, A. (Antonella), Munroe, P. (Patricia), Narisu, N. (Narisu), Ness, A.R. (Andrew), Northstone, K. (Kate), O'Rahilly, S. (Stephen), Purmann, C. (Carolin), Rees, M.G. (Matthew), Ridderstråle, M. (Martin), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Sandhu, M.S. (Manjinder), Saramies, J. (Jouko), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Sims, M.A. (Matthew), Song, K. (Kijoung), Stephens, J. (Jonathan), Stevens, S. (Suzanne), Stringham, H.M. (Heather), Tung, Y.C.L. (Loraine), Valle, T.T. (Timo), Tikka-Kleemola, P. (Päivi), Vimaleswaran, K.S. (Karani), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Watanabe, R.M. (Richard), Waterworth, D. (Dawn), Watkins, N. (Nicholas), Witteman, J.C.M. (Jacqueline), Zeggini, E. (Eleftheria), Zhai, G. (Guangju), Zillikens, M.C. (Carola), Altshuler, D. (David), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Farooqi, I.S. (Sadaf), Ferrucci, L. (Luigi), Guralnik, J.M. (Jack), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Laakso, M. (Markku), Mooser, V. (Vincent), Ong, K.K. (Ken), Ouwehand, W.H. (Willem), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Tuomi, T. (Tiinamaija), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Deloukas, P. (Panagiotis), Wareham, N.J. (Nick), Frayling, T.M. (Timothy), Groop, L. (Leif), Hayes, R.B. (Richard), Hunter, D. (David), Mohlke, K.L. (Karen), Peltonen, L. (Leena Johanna), Schlessinger, D. (David), Strachan, D.P. (David), Wichmann, H.E. (Erich), McCarthy, M.I. (Mark), Boehnke, M. (Michael), Barroso, I.E. (Inês), Abecasis, G.R. (Gonçalo), and Hirschhorn, J.N. (Joel)
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10-8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Published: 2009
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23. Interactive two-step training and management strategy for improvement of the quality of point-of-care testing by nurses:implementation of the strategy in blood glucose measurement

Author: Lehto, L. (Liisa), Ruokonen, A. (Aimo), and Liikanen, E. (Eeva)
Subjects: laadun parantaminen, ulkoinen laadunarviointi, hoitajat, external quality assessment, nurses, quality improvement, sisäinen laadun ohjaus, internal quality control, vieritestit, in-service training, blood glucose, toimipaikkakoulutus, point-of-care systems, verenglukoosi
Abstract: Point-of-care testing (POCT) is defined as laboratory tests performed outside the traditional clinical laboratory close to the patient at the time and place where care is received, such as hospitals and healthcare centers. The main reason for the use of POCT is that they provide rapid results and enable prompt interventions, with hopefully improved patient outcomes. All phases of laboratory procedure are included in POCT offering many opportunities for errors, which can influence on patients’ treatment. The measurements are more often performed by nurses than by laboratory professionals. These nurses have different kinds of professional backgrounds, e.g. public health nurses, registered and practical nurses, with minimal or no knowledge of laboratory procedures. The aim of the study was to develop a two-step training and management strategy for nurses to do POCT in hospital and primary healthcare center. In accordance with the strategy, with reasonable investment of laboratory resources, designated contact nurses were first trained in POCT by laboratory professionals, after which the contact nurses trained other nurses in POCT their respective units. Blood glucose, the most common point-of-care (POC) test, was chosen as an example to investigate the influence of training on the quality of the test performed by nurses. The quality of blood glucose measurements was studied by analyzing the control results obtained by nurses and biomedical laboratory scientists (BLSs). The study participants included nurses who were either untrained or trained to do POCT by using the developed interactive two-step training strategy. In conclusion, the nurses trained by using interactive two-step strategy achieved near-similar quality of blood glucose measurements as BLSs. The good quality of glucose measurements, once achieved by training, was also sustained in the long-term. Tiivistelmä Määritelmän mukaan vieritutkimuksiksi kutsutaan laboratoriotutkimuksia, joita tehdään perinteisen laboratorion ulkopuolella, tarvittaessa lähellä potilasta sairaalassa ja perusterveydenhuollon alueella. Pääasiassa vieritutkimuksia tehdään silloin kun tulos halutaan saada nopeasti ennen hoitopäätöstä tai tulevaa toimenpidettä. Vieritutkimusten tekeminen sisältää kaikki laboratoriotyön vaiheet ja jokaisessa vaiheessa on mahdollisuus tehdä virheitä, jotka voivat vaikuttaa potilaiden hoitoon. Laboratorioammattilaisten sijaan määrityksiä tekevät yhä useammin hoitajat sairaalan eri yksiköissä ja perusterveydenhuollon alueella. Näillä hoitajilla on erilainen ammatillinen peruskoulutus, kuten perushoitajan tai sairaanhoitajan koulutus, ja heillä on vähän tai ei ollenkaan tietoa laboratoriomenetelmistä. Tämän tutkimuksen tarkoituksena oli kehittää hoitajien vieritutkimustoimintaan koulutus- ja hallintomalli, joka toimisi sekä sairaalassa että terveyskeskuksessa. Strategian perusteena oli käyttää suhteellisen vähän laboratorioresursseja ja päästä silti hyvään laadulliseen lopputulokseen. Strategiaksi valittiin kaksiportainen, vuorovaikutteinen koulutusmalli, jossa laboratorioammattilaiset kouluttivat sairaalan ja perusterveydenhuollon yksiköissä ns. yhdyshenkilöt, jotka puolestaan kouluttivat edelleen oman yksikkönsä muut hoitajat tekemään vieritutkimuksia. Veren glukoosimääritys, joka on yleisin vieritutkimus, valittiin esimerkkitutkimukseksi tutkittaessa koulutuksen vaikutusta hoitajien tekemien vieritutkimusten laatuun. Veren glukoosimääritysten laatutasoa tutkittiin analysoimalla hoitajien ja laboratoriohoitajien tekemien kontrollinäytteiden tuloksia. Tutkimukseen osallistui hoitajia, jotka oli koulutettu kehitetyllä vuorovaikutteisella kaksiportaisella koulutusstrategialla vieritutkimusten tekemiseen, sekä hoitajia, jotka eivät olleet saaneet vastaavaa koulutusta. Koulutusmallin avulla hoitajien suorittamien vieritutkimusten laatu parani ja he saavuttivat lähes saman laatutason kuin laboratoriohoitajat. Hyvä, kerran saavutettu glukoosimääritysten laatutaso säilyi myös pitkällä aikajaksolla.
Published: 2014

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23 results on '"Ruokonen, A. (Aimo)"'

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23. Interactive two-step training and management strategy for improvement of the quality of point-of-care testing by nurses:implementation of the strategy in blood glucose measurement

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