Author: "Rudnicka, Alicja R." / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Rudnicka, Alicja R."' showing total 49 results

Start Over Author "Rudnicka, Alicja R." Database OAIster

49 results on '"Rudnicka, Alicja R."'

1. Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability (FOREVER)—A cohort study in a Danish high street optician setting:Design and methodology

Author: Freiberg, Josefine, Rovelt, Jens, Gazzard, Gus, Cour, Morten la, Kolko, Miriam, Torp‐Pedersen, Christian, Benn, Marianne, Brunak, Søren, Tolstrup, Janne, Toft‐Petersen, Anne Pernille, Burgdorf, Kristoffer Sølvsten, Banasik, Karina, Chmura, Piotr Jaroslaw, Thornit, Dorte Nellemann, Foster, Paul, Crabb, David P., Viswanathan, Ananth, Barman, Sarah, Owen, Christopher G., Rudnicka, Alicja R., Freiberg, Josefine, Rovelt, Jens, Gazzard, Gus, Cour, Morten la, Kolko, Miriam, Torp‐Pedersen, Christian, Benn, Marianne, Brunak, Søren, Tolstrup, Janne, Toft‐Petersen, Anne Pernille, Burgdorf, Kristoffer Sølvsten, Banasik, Karina, Chmura, Piotr Jaroslaw, Thornit, Dorte Nellemann, Foster, Paul, Crabb, David P., Viswanathan, Ananth, Barman, Sarah, Owen, Christopher G., and Rudnicka, Alicja R.
Abstract: Purpose The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). Design Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. Perspective The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.
Published: 2024

2. Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark

Author: Hudda, Mohammed T., Aarestrup, Julie, Owen, Christopher G., Cook, Derek G., Sorensen, Thorkild I. A., Rudnicka, Alicja R., Baker, Jennifer L., Whincup, Peter H., Nightingale, Claire M., Hudda, Mohammed T., Aarestrup, Julie, Owen, Christopher G., Cook, Derek G., Sorensen, Thorkild I. A., Rudnicka, Alicja R., Baker, Jennifer L., Whincup, Peter H., and Nightingale, Claire M.
Abstract: Importance Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR
Published: 2021

3. Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark

Author: Hudda, Mohammed T., Aarestrup, Julie, Owen, Christopher G., Cook, Derek G., Sorensen, Thorkild I. A., Rudnicka, Alicja R., Baker, Jennifer L., Whincup, Peter H., Nightingale, Claire M., Hudda, Mohammed T., Aarestrup, Julie, Owen, Christopher G., Cook, Derek G., Sorensen, Thorkild I. A., Rudnicka, Alicja R., Baker, Jennifer L., Whincup, Peter H., and Nightingale, Claire M.
Abstract: Importance Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR
Published: 2021

4. Sleep Duration and Risk of Type 2 Diabetes.

Author: Rudnicka, Alicja R, Rudnicka, Alicja R, Nightingale, Claire M, Donin, Angela S, Sattar, Naveed, Cook, Derek G, Whincup, Peter H, Owen, Christopher G, Rudnicka, Alicja R, Rudnicka, Alicja R, Nightingale, Claire M, Donin, Angela S, Sattar, Naveed, Cook, Derek G, Whincup, Peter H, and Owen, Christopher G
Abstract: BackgroundAssociations between sleep duration and type 2 diabetes (T2D) risk markers in childhood have been little studied. We examined associations between self-reported sleep duration and T2D risk markers in children.MethodsCross-sectional study of 4525 multiethnic UK children aged 9 to 10 years. Sleep time was calculated from self-reported usual time of going to bed and getting up on a school day, validated in a subset using accelerometers. Fasting blood samples provided levels of serum lipids and insulin, plasma glucose, and HbA1c. Physical measures included height, weight, bioimpedance, and blood pressure. Multilevel linear regression models of anthropometric, T2D, and cardiovascular risk markers with sleep duration were adjusted for sex, age, month, ethnicity, socioeconomic position, observer (physical measures only), and random effect of school.ResultsOn average, children slept 10.5 hours per night (95% range 8.0-12.0 hours). There were strong inverse graded relationships between sleep duration, adiposity, and diabetes risk markers. In adjusted models, a 1-hour-longer sleep duration was associated with 0.19 lower BMI (95% confidence interval [CI] 0.09 to 0.28), 0.03 kg/m5 lower fat mass index (95% CI 0.00 to 0.05 kg/m5), 2.9% lower homeostasis model assessment insulin resistance (95% CI 1.2% to 4.4%), and 0.24% lower fasting glucose (95% CI 0.03% to 0.44%); there was no association with HbA1c or cardiovascular risk. Associations with insulin and glucose remained after an additional adjustment for adiposity markers.ConclusionsThe finding of an inverse association between sleep duration and T2D risk markers in childhood is novel. Intervention studies are needed to establish the causality of these associations, which could provide a simple strategy for early T2D prevention.
Published: 2017

5. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

Author: Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., Owen, Christopher G., Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., and Owen, Christopher G.
Abstract: The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.
Published: 2016

6. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

Author: Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., Owen, Christopher G., Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., and Owen, Christopher G.
Abstract: The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.
Published: 2016

7. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

Author: Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., Owen, Christopher G., Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., and Owen, Christopher G.
Abstract: The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.
Published: 2016

8. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

Author: Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., Owen, Christopher G., Rudnicka, Alicja R., Kapetanakis, Venediktos V., Wathern, Andrea K., Logan, Nicola S., Gilmartin, Bernard, Whincup, Peter H., Cook, Derek G., and Owen, Christopher G.
Abstract: The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.
Published: 2016

9. Risk factors for childhood myopia:findings from the NICER study

Author: O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., Rudnicka, Alicja R., O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., and Rudnicka, Alicja R.
Abstract: PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.
Published: 2015

10. Risk factors for childhood myopia:findings from the NICER study

Author: O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., Rudnicka, Alicja R., O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., and Rudnicka, Alicja R.
Abstract: PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.
Published: 2015

11. Risk factors for childhood myopia:findings from the NICER study

Author: O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., Rudnicka, Alicja R., O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., and Rudnicka, Alicja R.
Abstract: PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.
Published: 2015

12. Risk factors for childhood myopia:findings from the NICER study

Author: O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., Rudnicka, Alicja R., O’Donoghue, Lisa, Kapetanankis, Venediktos V., McClelland, Julie F., Logan, Nicola S., Owen, Christopher G., Saunders, Kathryn J., and Rudnicka, Alicja R.
Abstract: PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.
Published: 2015

13. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, London, Stephanie J, Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, and London, Stephanie J
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014
Full Text: View/download PDF

14. No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

Author: Meyre, David, Baumert, Jens, Huang, Jie, McKnight, Barbara, Sabater-Lleal, Maria, Steri, Maristella, Chu, Audrey Y., Trompet, Stella, Lopez, Lorna M., Fornage, Myriam, Teumer, Alexander, Tang, Weihong, Rudnicka, Alicja R., Mälarstig, Anders, Hottenga, Jouke-Jan, Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, Jennifer E., Morange, Pierre-Emmanuel, Rose, Lynda M., Basu, Saonli, Rumley, Ann, Stott, David J., Buckley, Brendan M., de Craen, Anton J. M., Sanna, Serena, Masala, Marco, Biffar, Reiner, Homuth, Georg, Silveira, Angela, Sennblad, Bengt, Goel, Anuj, Watkins, Hugh, Müller-Nurasyid, Martina, Rückerl, Regina, Taylor, Kent, Chen, Ming-Huei, de Geus, Eco J. C., Hofman, Albert, Witteman, Jacqueline C. M., de Maat, Moniek P. M., Palotie, Aarno, Davies, Gail, Siscovick, David S., Kolcic, Ivana, Wild, Sarah H., Song, Jaejoon, McArdle, Wendy L., Ford, Ian, Sattar, Naveed, Schlessinger, David, Grotevendt, Anne, Franzosi, Maria Grazia, Illig, Thomas, Waldenberger, Melanie, Lumley, Thomas, Tofler, Geoffrey H., Willemsen, Gonneke, Uitterlinden, André G., Rivadeneira, Fernando, Räikkönen, Katri, Chasman, Daniel I., Folsom, Aaron R., Lowe, Gordon D., Westendorp, Rudi G. J., Slagboom, P. Eline, Cucca, Francesco, Wallaschofski, Henri, Strawbridge, Rona J., Seedorf, Udo, Koenig, Wolfgang, Bis, Joshua C., Mukamal, Kenneth J., van Dongen, Jenny, Widen, Elisabeth, Franco, Oscar H., Starr, John M., Liu, Kiang, Ferrucci, Luigi, Polasek, Ozren, Wilson, James F., Oudot-Mellakh, Tiphaine, Campbell, Harry, Navarro, Pau, Bandinelli, Stefania, Eriksson, Johan, Boomsma, Dorret I., Dehghan, Abbas, Clarke, Robert, Hamsten, Anders, Boerwinkle, Eric, Jukema, J. Wouter, Naitza, Silvia, Ridker, Paul M., Völzke, Henry, Deary, Ian J., Reiner, Alexander P., Trégouët, David-Alexandre, O'Donnell, Christopher J., Strachan, David P., Peters, Annette, Smith, Nicholas L., Meyre, David, Baumert, Jens, Huang, Jie, McKnight, Barbara, Sabater-Lleal, Maria, Steri, Maristella, Chu, Audrey Y., Trompet, Stella, Lopez, Lorna M., Fornage, Myriam, Teumer, Alexander, Tang, Weihong, Rudnicka, Alicja R., Mälarstig, Anders, Hottenga, Jouke-Jan, Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, Jennifer E., Morange, Pierre-Emmanuel, Rose, Lynda M., Basu, Saonli, Rumley, Ann, Stott, David J., Buckley, Brendan M., de Craen, Anton J. M., Sanna, Serena, Masala, Marco, Biffar, Reiner, Homuth, Georg, Silveira, Angela, Sennblad, Bengt, Goel, Anuj, Watkins, Hugh, Müller-Nurasyid, Martina, Rückerl, Regina, Taylor, Kent, Chen, Ming-Huei, de Geus, Eco J. C., Hofman, Albert, Witteman, Jacqueline C. M., de Maat, Moniek P. M., Palotie, Aarno, Davies, Gail, Siscovick, David S., Kolcic, Ivana, Wild, Sarah H., Song, Jaejoon, McArdle, Wendy L., Ford, Ian, Sattar, Naveed, Schlessinger, David, Grotevendt, Anne, Franzosi, Maria Grazia, Illig, Thomas, Waldenberger, Melanie, Lumley, Thomas, Tofler, Geoffrey H., Willemsen, Gonneke, Uitterlinden, André G., Rivadeneira, Fernando, Räikkönen, Katri, Chasman, Daniel I., Folsom, Aaron R., Lowe, Gordon D., Westendorp, Rudi G. J., Slagboom, P. Eline, Cucca, Francesco, Wallaschofski, Henri, Strawbridge, Rona J., Seedorf, Udo, Koenig, Wolfgang, Bis, Joshua C., Mukamal, Kenneth J., van Dongen, Jenny, Widen, Elisabeth, Franco, Oscar H., Starr, John M., Liu, Kiang, Ferrucci, Luigi, Polasek, Ozren, Wilson, James F., Oudot-Mellakh, Tiphaine, Campbell, Harry, Navarro, Pau, Bandinelli, Stefania, Eriksson, Johan, Boomsma, Dorret I., Dehghan, Abbas, Clarke, Robert, Hamsten, Anders, Boerwinkle, Eric, Jukema, J. Wouter, Naitza, Silvia, Ridker, Paul M., Völzke, Henry, Deary, Ian J., Reiner, Alexander P., Trégouët, David-Alexandre, O'Donnell, Christopher J., Strachan, David P., Peters, Annette, and Smith, Nicholas L.
Abstract: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10−8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.
Published: 2014

15. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, London, Stephanie J, Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, and London, Stephanie J
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014

16. No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

Author: Meyre, David, Baumert, Jens, Huang, Jie, McKnight, Barbara, Sabater-Lleal, Maria, Steri, Maristella, Chu, Audrey Y., Trompet, Stella, Lopez, Lorna M., Fornage, Myriam, Teumer, Alexander, Tang, Weihong, Rudnicka, Alicja R., Mälarstig, Anders, Hottenga, Jouke-Jan, Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, Jennifer E., Morange, Pierre-Emmanuel, Rose, Lynda M., Basu, Saonli, Rumley, Ann, Stott, David J., Buckley, Brendan M., de Craen, Anton J. M., Sanna, Serena, Masala, Marco, Biffar, Reiner, Homuth, Georg, Silveira, Angela, Sennblad, Bengt, Goel, Anuj, Watkins, Hugh, Müller-Nurasyid, Martina, Rückerl, Regina, Taylor, Kent, Chen, Ming-Huei, de Geus, Eco J. C., Hofman, Albert, Witteman, Jacqueline C. M., de Maat, Moniek P. M., Palotie, Aarno, Davies, Gail, Siscovick, David S., Kolcic, Ivana, Wild, Sarah H., Song, Jaejoon, McArdle, Wendy L., Ford, Ian, Sattar, Naveed, Schlessinger, David, Grotevendt, Anne, Franzosi, Maria Grazia, Illig, Thomas, Waldenberger, Melanie, Lumley, Thomas, Tofler, Geoffrey H., Willemsen, Gonneke, Uitterlinden, André G., Rivadeneira, Fernando, Räikkönen, Katri, Chasman, Daniel I., Folsom, Aaron R., Lowe, Gordon D., Westendorp, Rudi G. J., Slagboom, P. Eline, Cucca, Francesco, Wallaschofski, Henri, Strawbridge, Rona J., Seedorf, Udo, Koenig, Wolfgang, Bis, Joshua C., Mukamal, Kenneth J., van Dongen, Jenny, Widen, Elisabeth, Franco, Oscar H., Starr, John M., Liu, Kiang, Ferrucci, Luigi, Polasek, Ozren, Wilson, James F., Oudot-Mellakh, Tiphaine, Campbell, Harry, Navarro, Pau, Bandinelli, Stefania, Eriksson, Johan, Boomsma, Dorret I., Dehghan, Abbas, Clarke, Robert, Hamsten, Anders, Boerwinkle, Eric, Jukema, J. Wouter, Naitza, Silvia, Ridker, Paul M., Völzke, Henry, Deary, Ian J., Reiner, Alexander P., Trégouët, David-Alexandre, O'Donnell, Christopher J., Strachan, David P., Peters, Annette, Smith, Nicholas L., Meyre, David, Baumert, Jens, Huang, Jie, McKnight, Barbara, Sabater-Lleal, Maria, Steri, Maristella, Chu, Audrey Y., Trompet, Stella, Lopez, Lorna M., Fornage, Myriam, Teumer, Alexander, Tang, Weihong, Rudnicka, Alicja R., Mälarstig, Anders, Hottenga, Jouke-Jan, Kavousi, Maryam, Lahti, Jari, Tanaka, Toshiko, Hayward, Caroline, Huffman, Jennifer E., Morange, Pierre-Emmanuel, Rose, Lynda M., Basu, Saonli, Rumley, Ann, Stott, David J., Buckley, Brendan M., de Craen, Anton J. M., Sanna, Serena, Masala, Marco, Biffar, Reiner, Homuth, Georg, Silveira, Angela, Sennblad, Bengt, Goel, Anuj, Watkins, Hugh, Müller-Nurasyid, Martina, Rückerl, Regina, Taylor, Kent, Chen, Ming-Huei, de Geus, Eco J. C., Hofman, Albert, Witteman, Jacqueline C. M., de Maat, Moniek P. M., Palotie, Aarno, Davies, Gail, Siscovick, David S., Kolcic, Ivana, Wild, Sarah H., Song, Jaejoon, McArdle, Wendy L., Ford, Ian, Sattar, Naveed, Schlessinger, David, Grotevendt, Anne, Franzosi, Maria Grazia, Illig, Thomas, Waldenberger, Melanie, Lumley, Thomas, Tofler, Geoffrey H., Willemsen, Gonneke, Uitterlinden, André G., Rivadeneira, Fernando, Räikkönen, Katri, Chasman, Daniel I., Folsom, Aaron R., Lowe, Gordon D., Westendorp, Rudi G. J., Slagboom, P. Eline, Cucca, Francesco, Wallaschofski, Henri, Strawbridge, Rona J., Seedorf, Udo, Koenig, Wolfgang, Bis, Joshua C., Mukamal, Kenneth J., van Dongen, Jenny, Widen, Elisabeth, Franco, Oscar H., Starr, John M., Liu, Kiang, Ferrucci, Luigi, Polasek, Ozren, Wilson, James F., Oudot-Mellakh, Tiphaine, Campbell, Harry, Navarro, Pau, Bandinelli, Stefania, Eriksson, Johan, Boomsma, Dorret I., Dehghan, Abbas, Clarke, Robert, Hamsten, Anders, Boerwinkle, Eric, Jukema, J. Wouter, Naitza, Silvia, Ridker, Paul M., Völzke, Henry, Deary, Ian J., Reiner, Alexander P., Trégouët, David-Alexandre, O'Donnell, Christopher J., Strachan, David P., Peters, Annette, and Smith, Nicholas L.
Abstract: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10−8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.
Published: 2014

17. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, London, Stephanie J, Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce B J, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, Ripatti, Samuli, Scott, Rodney J, Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C, Starr, John M, Wijmenga, Cisca, Minster, Ryan L, Lederer, David J, Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P, Gläser, Sven, Hammond, Christopher J, Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B, Gudnason, Vilmundur, Hancock, Dana B, Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F, Wjst, Matthias, Kim, Woo Jin, Porteous, David J, Scotland, Generation, Smith, Blair H, Viljanen, Anne, Heliövaara, Markku, Attia, John R, Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H, Teumer, Alexander, Spector, Timothy D, Melén, Erik, Peters, Marjolein J, Lange, Leslie A, Barr, R Graham, Bracke, Ken R, Verhamme, Fien M, Sung, Joohon, Hiemstra, Pieter S, Cassano, Patricia A, Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P, Brusselle, Guy G, Tobin, Martin D, and London, Stephanie J
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014

18. Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., and Saunders, Kathryn J.
Abstract: Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.
Published: 2013

19. Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., and Saunders, Kathryn J.
Abstract: Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.
Published: 2013

20. Multiethnic Meta-Analysis of Genome-Wide Association Studies in >100 000 Subjects Identifies 23 Fibrinogen-Associated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

Author: Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, O’Donnell, Christopher J., Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, and O’Donnell, Christopher J.
Abstract: Background: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and results: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013

21. Multiethnic Meta-Analysis of Genome-Wide Association Studies in >100 000 Subjects Identifies 23 Fibrinogen-Associated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

Author: Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, O’Donnell, Christopher J., Sabater-Lleal, Maria, Huang, Jie, Chasman, Daniel, Naitza, Silvia, Dehghan, Abbas, Johnson, Andrew D., Teumer, Alexander, Reiner, Alex P., Folkersen, Lasse, Basu, Saonli, Rudnicka, Alicja R., Trompet, Stella, Mälarstig, Anders, Baumert, Jens, Bis, Joshua C., Guo, Xiuqing, Hottenga, Jouke J., Shin, So-Youn, Lopez, Lorna M., Lahti, Jari, Tanaka, Toshiko, Yanek, Lisa R., Oudot-Mellakh, Tiphaine, Wilson, James F., Navarro, Pau, Huffman, Jennifer E., Zemunik, Tatijana, Redline, Susan, Mehra, Reena, Pulanic, Drazen, Rudan, Igor, Wright, Alan F., Kolcic, Ivana, Polasek, Ozren, Wild, Sarah H., Campbell, Harry, Curb, J. David, Wallace, Robert, Liu, Simin, Eaton, Charles B., Becker, Diane M., Becker, Lewis C., Bandinelli, Stefania, Räikkönen, Katri, Widen, Elisabeth, Palotie, Aarno, Fornage, Myriam, Green, David, Gross, Myron, Davies, Gail, Harris, Sarah E., Liewald, David C., Starr, John M., Williams, Frances M.K., Grant, Peter J., Spector, Timothy D., Strawbridge, Rona J., Silveira, Angela, Sennblad, Bengt, Rivadeneira, Fernando, Uitterlinden, Andre G., Franco, Oscar H., Hofman, Albert, van Dongen, Jenny, Willemsen, Gonneke, Boomsma, Dorret I., Yao, Jie, Swords Jenny, Nancy, Haritunians, Talin, McKnight, Barbara, Lumley, Thomas, Taylor, Kent D., Rotter, Jerome I., Psaty, Bruce M., Peters, Annette, Gieger, Christian, Illig, Thomas, Grotevendt, Anne, Homuth, Georg, Völzke, Henry, Kocher, Thomas, Goel, Anuj, Franzosi, Maria Grazia, Seedorf, Udo, Clarke, Robert, Steri, Maristella, Tarasov, Kirill V., Sanna, Serena, Schlessinger, David, Stott, David J., Sattar, Naveed, Buckley, Brendan M., Rumley, Ann, Lowe, Gordon D., McArdle, Wendy L., Chen, Ming-Huei, Tofler, Geoffrey H., Song, Jaejoon, Boerwinkle, Eric, Folsom, Aaron R., Rose, Lynda M., Franco-Cereceda, Anders, Teichert, Martina, Ikram, M. Arfan, Mosley, Thomas H., Bevan, Steve, Dichgans, Martin, Rothwell, Peter M., Sudlow, Cathie L.M., Hopewell, Jemma C., Chambers, John C., Saleheen, Danish, Kooner, Jaspal S., Danesh, John, Nelson, Christopher P., Erdmann, Jeanette, Reilly, Muredach P., Kathiresan, Sekar, Schunkert, Heribert, Morange, Pierre-Emmanuel, Ferrucci, Luigi, Eriksson, Johan G., Jacobs, David, Deary, Ian J., Soranzo, Nicole, Witteman, Jacqueline C.M., de Geus, Eco J.C., Tracy, Russell P., Hayward, Caroline, Koenig, Wolfgang, Cucca, Francesco, Jukema, J. Wouter, Eriksson, Per, Seshadri, Sudha, Markus, Hugh S., Watkins, Hugh, Samani, Nilesh J., Wallaschofski, Henri, Smith, Nicholas L., Tregouet, David, Ridker, Paul M, Tang, Weihong, Strachan, David P., Hamsten, Anders, and O’Donnell, Christopher J.
Abstract: Background: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and results: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013

22. Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., and Saunders, Kathryn J.
Abstract: Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.
Published: 2013

23. Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola S., Rudnicka, Alicja R., Owen, Chris G., and Saunders, Kathryn J.
Abstract: Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.
Published: 2013

24. Visual acuity measures do not reliably detect childhood refractive error - an epidemiological study

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., and Saunders, Kathryn J.
Abstract: Purpose To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. Methods The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. Results Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. Conclusions Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.
Published: 2012

25. Visual acuity measures do not reliably detect childhood refractive error - an epidemiological study

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., and Saunders, Kathryn J.
Abstract: Purpose To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. Methods The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. Results Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. Conclusions Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.
Published: 2012

26. Visual acuity measures do not reliably detect childhood refractive error - an epidemiological study

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., and Saunders, Kathryn J.
Abstract: Purpose To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. Methods The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. Results Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. Conclusions Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.
Published: 2012

27. Visual acuity measures do not reliably detect childhood refractive error - an epidemiological study

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S., and Saunders, Kathryn J.
Abstract: Purpose To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. Methods The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. Results Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. Conclusions Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.
Published: 2012

28. A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Author: Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, and Hall, Ian P.
Abstract: Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.
Published: 2011
Full Text: View/download PDF

29. Refractive and corneal astigmatism in white school children in Northern Ireland

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, and Saunders, Kathryn J.
Abstract: To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error.
Published: 2011

30. Refractive and corneal astigmatism in white school children in Northern Ireland

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, and Saunders, Kathryn J.
Abstract: To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error.
Published: 2011

31. A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample

Author: University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Asa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., SpiroMeta Consortium, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Public Health, Obeidat, Ma'en, Wain, Louise V., Shrine, Nick, Kalsheker, Noor, Artigas, Maria Soler, Repapi, Emmanouela, Burton, Paul R., Johnson, Toby, Ramasamy, Adaikalavan, Zhao, Jing Hua, Zhai, Guangju, Huffman, Jennifer E., Vitart, Veronique, Albrecht, Eva, Igl, Wilmar, Hartikainen, Anna-Liisa, Pouta, Anneli, Cadby, Gemma, Hui, Jennie, Palmer, Lyle J., Hadley, David, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Deloukas, Panos, Granell, Raquel, Henderson, John, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Polasek, Ozren, Rudan, Igor, Wright, Alan F., Campbell, Harry, Wild, Sarah H., Wilson, James F., Heinrich, Joachim, Imboden, Medea, Probst-Hensch, Nicole M., Gyllensten, Ulf, Johansson, Asa, Zaboli, Ghazal, Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Kaprio, Jaakko, Jarvelin, Marjo-Riitta, Hayward, Caroline, Evans, David M., Koch, Beate, Musk, Arthur William, Elliott, Paul, Strachan, David P., Tobin, Martin D., Sayers, Ian, Hall, Ian P., and SpiroMeta Consortium
Abstract: RATIONALE: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). OBJECTIVES: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. METHODS: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. RESULTS: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers. CONCLUSIONS: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.
Published: 2011

32. Genetic Predictors of Fibrin D-Dimer Levels in Healthy Adults

Author: Smith, Nicholas L., Huffman, Jennifer E., Strachan, David P., Huang, Jie, Dehghan, Abbas, Trompet, Stella, Lopez, Lorna M., Shin, So-Youn, Baumert, Jens, Vitart, Veronique, Bis, Joshua C., Wild, Sarah H., Rumley, Ann, Yang, Qiong, Uitterlinden, Andre G., Stott, David. J., Davies, Gail, Carter, Angela M., Thorand, Barbara, Polašek, Ozren, McKnight, Barbara, Campbell, Harry, Rudnicka, Alicja R., Chen, Ming-Huei, Buckley, Brendan M., Harris, Sarah E., Peters, Annette, Pulanic, Drazen, Lumley, Thomas, de Craen, Anton J.M., Liewald, David C., Gieger, Christian, Campbell, Susan, Ford, Ian, Gow, Alan J., Luciano, Michelle, Porteous, David J., Guo, Xiuqing, Sattar, Naveed, Tenesa, Albert, Cushman, Mary, Slagboom, P. Eline, Visscher, Peter M., Spector, Tim D., Illig, Thomas, Rudan, Igor, Bovill, Edwin G., Wright, Alan F., McArdle, Wendy L., Tofler, Geoffrey, Hofman, Albert, Westendorp, Rudi G.J., Starr, John M., Grant, Peter J., Karakas, Mahir, Hastie, Nicholas D., Psaty, Bruce M., Wilson, James F., Lowe, Gordon D.O., O'Donnell, Christopher J., Witteman, Jacqueline C.M., Jukema, J. Wouter, Deary, Ian J., Soranzo, Nicole, Koenig, Wolfgang, Hayward, Caroline, Smith, Nicholas L., Huffman, Jennifer E., Strachan, David P., Huang, Jie, Dehghan, Abbas, Trompet, Stella, Lopez, Lorna M., Shin, So-Youn, Baumert, Jens, Vitart, Veronique, Bis, Joshua C., Wild, Sarah H., Rumley, Ann, Yang, Qiong, Uitterlinden, Andre G., Stott, David. J., Davies, Gail, Carter, Angela M., Thorand, Barbara, Polašek, Ozren, McKnight, Barbara, Campbell, Harry, Rudnicka, Alicja R., Chen, Ming-Huei, Buckley, Brendan M., Harris, Sarah E., Peters, Annette, Pulanic, Drazen, Lumley, Thomas, de Craen, Anton J.M., Liewald, David C., Gieger, Christian, Campbell, Susan, Ford, Ian, Gow, Alan J., Luciano, Michelle, Porteous, David J., Guo, Xiuqing, Sattar, Naveed, Tenesa, Albert, Cushman, Mary, Slagboom, P. Eline, Visscher, Peter M., Spector, Tim D., Illig, Thomas, Rudan, Igor, Bovill, Edwin G., Wright, Alan F., McArdle, Wendy L., Tofler, Geoffrey, Hofman, Albert, Westendorp, Rudi G.J., Starr, John M., Grant, Peter J., Karakas, Mahir, Hastie, Nicholas D., Psaty, Bruce M., Wilson, James F., Lowe, Gordon D.O., O'Donnell, Christopher J., Witteman, Jacqueline C.M., Jukema, J. Wouter, Deary, Ian J., Soranzo, Nicole, Koenig, Wolfgang, and Hayward, Caroline
Abstract: Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between ≈2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log–transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4×10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4×10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9×10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log–transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported.
Published: 2011

33. Genetic Predictors of Fibrin D-Dimer Levels in Healthy Adults

Author: Smith, Nicholas L., Huffman, Jennifer E., Strachan, David P., Huang, Jie, Dehghan, Abbas, Trompet, Stella, Lopez, Lorna M., Shin, So-Youn, Baumert, Jens, Vitart, Veronique, Bis, Joshua C., Wild, Sarah H., Rumley, Ann, Yang, Qiong, Uitterlinden, Andre G., Stott, David. J., Davies, Gail, Carter, Angela M., Thorand, Barbara, Polašek, Ozren, McKnight, Barbara, Campbell, Harry, Rudnicka, Alicja R., Chen, Ming-Huei, Buckley, Brendan M., Harris, Sarah E., Peters, Annette, Pulanic, Drazen, Lumley, Thomas, de Craen, Anton J.M., Liewald, David C., Gieger, Christian, Campbell, Susan, Ford, Ian, Gow, Alan J., Luciano, Michelle, Porteous, David J., Guo, Xiuqing, Sattar, Naveed, Tenesa, Albert, Cushman, Mary, Slagboom, P. Eline, Visscher, Peter M., Spector, Tim D., Illig, Thomas, Rudan, Igor, Bovill, Edwin G., Wright, Alan F., McArdle, Wendy L., Tofler, Geoffrey, Hofman, Albert, Westendorp, Rudi G.J., Starr, John M., Grant, Peter J., Karakas, Mahir, Hastie, Nicholas D., Psaty, Bruce M., Wilson, James F., Lowe, Gordon D.O., O'Donnell, Christopher J., Witteman, Jacqueline C.M., Jukema, J. Wouter, Deary, Ian J., Soranzo, Nicole, Koenig, Wolfgang, Hayward, Caroline, Smith, Nicholas L., Huffman, Jennifer E., Strachan, David P., Huang, Jie, Dehghan, Abbas, Trompet, Stella, Lopez, Lorna M., Shin, So-Youn, Baumert, Jens, Vitart, Veronique, Bis, Joshua C., Wild, Sarah H., Rumley, Ann, Yang, Qiong, Uitterlinden, Andre G., Stott, David. J., Davies, Gail, Carter, Angela M., Thorand, Barbara, Polašek, Ozren, McKnight, Barbara, Campbell, Harry, Rudnicka, Alicja R., Chen, Ming-Huei, Buckley, Brendan M., Harris, Sarah E., Peters, Annette, Pulanic, Drazen, Lumley, Thomas, de Craen, Anton J.M., Liewald, David C., Gieger, Christian, Campbell, Susan, Ford, Ian, Gow, Alan J., Luciano, Michelle, Porteous, David J., Guo, Xiuqing, Sattar, Naveed, Tenesa, Albert, Cushman, Mary, Slagboom, P. Eline, Visscher, Peter M., Spector, Tim D., Illig, Thomas, Rudan, Igor, Bovill, Edwin G., Wright, Alan F., McArdle, Wendy L., Tofler, Geoffrey, Hofman, Albert, Westendorp, Rudi G.J., Starr, John M., Grant, Peter J., Karakas, Mahir, Hastie, Nicholas D., Psaty, Bruce M., Wilson, James F., Lowe, Gordon D.O., O'Donnell, Christopher J., Witteman, Jacqueline C.M., Jukema, J. Wouter, Deary, Ian J., Soranzo, Nicole, Koenig, Wolfgang, and Hayward, Caroline
Abstract: Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between ≈2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log–transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4×10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4×10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9×10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log–transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported.
Published: 2011

34. Refractive and corneal astigmatism in white school children in Northern Ireland

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, and Saunders, Kathryn J.
Abstract: To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error.
Published: 2011

35. Refractive and corneal astigmatism in white school children in Northern Ireland

Author: O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, Saunders, Kathryn J., O'Donoghue, Lisa, Rudnicka, Alicja R., McClelland, Julie F., Logan, Nicola S, Owen, Christopher, and Saunders, Kathryn J.
Abstract: To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error.
Published: 2011

36. Genome-wide association study identifies five loci associated with lung function

Author: Repapi, Emmanouela, Sayers, Ian, Wain, Louise V., Burton, Paul R., Johnson, Toby, Obeidat, Ma'en, Zhao, Jing Hua, Ramasamy, Adaikalavan, Zhai, Guangju, Vitart, Veronique, Huffman, Jennifer E., Igl, Wilmar, Albrecht, Eva, Deloukas, Panos, Henderson, John, Granell, Raquel, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Imboden, Medea, Wichmann, H. Erich, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Hartikainen, Anna-Liisa, Peltonen, Leena, Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Campbell, Harry, Wild, Sarah H., Wilson, James F., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Polasek, Ozren, Rudan, Igor, Wright, Alan F., Heliovaara, Markku, Ripatti, Samuli, Pouta, Anneli, Naluai, Asa Torinsson, Olin, Anna-Carin, Torén, Kjell, Cooper, Matthew N., James, Alan L., Palmer, Lyle J., Hingorani, Aroon D., Wannamethee, S. Goya, Whincup, Peter H., Smith, George Davey, Ebrahim, Shah, McKeever, Tricia M., Pavord, Ian D., MacLeod, Andrew K., Morris, Andrew D., Porteous, David J., Cooper, Cyrus, Dennison, Elaine, Shaheen, Seif, Karrasch, Stefan, Schnabel, Eva, Schulz, Holger, Grallert, Harald, Bouatia-Naji, Nabila, Delplanque, Jerome, Froguel, Philippe, Blakey, John D., Britton, John R., Morris, Richard W., Holloway, John W., Lawlor, Debbie A., Hui, Jennie, Nyberg, Fredrik, Jarvelin, Marjo-Riitta, Jackson, Cathy, Kahonen, Mika, Kaprio, Jaakko, Probst-Hensch, Nicole M., Koch, Beate, Hayward, Caroline, Evans, David M., Elliott, Paul, Strachan, David P., Hall, Ian P., Tobin, Martin D., Repapi, Emmanouela, Sayers, Ian, Wain, Louise V., Burton, Paul R., Johnson, Toby, Obeidat, Ma'en, Zhao, Jing Hua, Ramasamy, Adaikalavan, Zhai, Guangju, Vitart, Veronique, Huffman, Jennifer E., Igl, Wilmar, Albrecht, Eva, Deloukas, Panos, Henderson, John, Granell, Raquel, McArdle, Wendy L., Rudnicka, Alicja R., Barroso, Ines, Loos, Ruth J. F., Wareham, Nicholas J., Mustelin, Linda, Rantanen, Taina, Surakka, Ida, Imboden, Medea, Wichmann, H. Erich, Grkovic, Ivica, Jankovic, Stipan, Zgaga, Lina, Hartikainen, Anna-Liisa, Peltonen, Leena, Gyllensten, Ulf, Johansson, Åsa, Zaboli, Ghazal, Campbell, Harry, Wild, Sarah H., Wilson, James F., Glaeser, Sven, Homuth, Georg, Voelzke, Henry, Mangino, Massimo, Soranzo, Nicole, Spector, Tim D., Polasek, Ozren, Rudan, Igor, Wright, Alan F., Heliovaara, Markku, Ripatti, Samuli, Pouta, Anneli, Naluai, Asa Torinsson, Olin, Anna-Carin, Torén, Kjell, Cooper, Matthew N., James, Alan L., Palmer, Lyle J., Hingorani, Aroon D., Wannamethee, S. Goya, Whincup, Peter H., Smith, George Davey, Ebrahim, Shah, McKeever, Tricia M., Pavord, Ian D., MacLeod, Andrew K., Morris, Andrew D., Porteous, David J., Cooper, Cyrus, Dennison, Elaine, Shaheen, Seif, Karrasch, Stefan, Schnabel, Eva, Schulz, Holger, Grallert, Harald, Bouatia-Naji, Nabila, Delplanque, Jerome, Froguel, Philippe, Blakey, John D., Britton, John R., Morris, Richard W., Holloway, John W., Lawlor, Debbie A., Hui, Jennie, Nyberg, Fredrik, Jarvelin, Marjo-Riitta, Jackson, Cathy, Kahonen, Mika, Kaprio, Jaakko, Probst-Hensch, Nicole M., Koch, Beate, Hayward, Caroline, Evans, David M., Elliott, Paul, Strachan, David P., Hall, Ian P., and Tobin, Martin D.
Abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
Published: 2010
Full Text: View/download PDF

37. Refractive error and visual impairment in school children in Northern Ireland

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, and Saunders, Kathryn J.
Abstract: To describe the prevalence of refractive error (myopia and hyperopia) and visual impairment in a representative sample of white school children.
Published: 2010

38. Refractive error and visual impairment in school children in Northern Ireland

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, and Saunders, Kathryn J.
Abstract: To describe the prevalence of refractive error (myopia and hyperopia) and visual impairment in a representative sample of white school children.
Published: 2010

39. Refractive error and visual impairment in school children in Northern Ireland

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, and Saunders, Kathryn J.
Abstract: To describe the prevalence of refractive error (myopia and hyperopia) and visual impairment in a representative sample of white school children.
Published: 2010

40. Refractive error and visual impairment in school children in Northern Ireland

Author: O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, Saunders, Kathryn J., O'Donoghue, Lisa, McClelland, Julie F., Logan, Nicola, Rudnicka, Alicja R., Owen, Christopher G, and Saunders, Kathryn J.
Abstract: To describe the prevalence of refractive error (myopia and hyperopia) and visual impairment in a representative sample of white school children.
Published: 2010

41. Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative review of the evidence.

Author: Owen, Christopher G, Whincup, Peter H, Kaye, Samantha J, Martin, Richard M, Davey Smith, George, Cook, Derek G, Bergstrom, Erik, Black, Stephanie, Wadsworth, Michael E J, Fall, Caroline H, Freudenheim, Jo L, Nie, Jing, Huxley, Rachel R, Kolacek, Sanja, Leeson, C Paul, Pearce, Mark S, Raitakari, Olli T, Lisinen, Irina, Viikari, Jorma S, Ravelli, Anita C, Rudnicka, Alicja R, Strachan, David P, Williams, Sheila M, Owen, Christopher G, Whincup, Peter H, Kaye, Samantha J, Martin, Richard M, Davey Smith, George, Cook, Derek G, Bergstrom, Erik, Black, Stephanie, Wadsworth, Michael E J, Fall, Caroline H, Freudenheim, Jo L, Nie, Jing, Huxley, Rachel R, Kolacek, Sanja, Leeson, C Paul, Pearce, Mark S, Raitakari, Olli T, Lisinen, Irina, Viikari, Jorma S, Ravelli, Anita C, Rudnicka, Alicja R, Strachan, David P, and Williams, Sheila M
Abstract: BACKGROUND: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism. OBJECTIVE: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood. DESIGN: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined. RESULTS: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates. CONCLUSIONS: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.
Published: 2008

42. Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative review of the evidence

Author: Owen, Christopher G., Whincup, Peter H., Kaye, Samantha J., Martin, Richard M., Smith, George Davey, Cook, Derek G., Bergstrom, Erik, Black, Stephanie, Wadsworth, Michael E. J., Fall, Caroline H., Freudenheim, Jo L., Nie, Jing, Huxley, Rachel R., Kolacek, Sanja, Leeson, C. Paul, Pearce, Mark S., Raitakari, Olli T., Lisinen, Irina, Viikari, Jorma S., Ravelli, Anita C., Rudnicka, Alicja R., Strachan, David P., Williams, Sheila M., Owen, Christopher G., Whincup, Peter H., Kaye, Samantha J., Martin, Richard M., Smith, George Davey, Cook, Derek G., Bergstrom, Erik, Black, Stephanie, Wadsworth, Michael E. J., Fall, Caroline H., Freudenheim, Jo L., Nie, Jing, Huxley, Rachel R., Kolacek, Sanja, Leeson, C. Paul, Pearce, Mark S., Raitakari, Olli T., Lisinen, Irina, Viikari, Jorma S., Ravelli, Anita C., Rudnicka, Alicja R., Strachan, David P., and Williams, Sheila M.
Published: 2008

43. Lifecourse influences on health among British adults: Effects of region of residence in childhood and adulthood.

Author: Strachan, David. P, Rudnicka, Alicja. R, Power, Chris, Shepherd, Peter, Fuller, Elizabeth, Davis, Adrian, Gibb, Ian, Kumari, Meena, Rumley, Anne, Macfarlane, Gary. J, Rahi, Jugnoo, Stansfeld, Stephen, Rodgers, Bryan, Strachan, David. P, Rudnicka, Alicja. R, Power, Chris, Shepherd, Peter, Fuller, Elizabeth, Davis, Adrian, Gibb, Ian, Kumari, Meena, Rumley, Anne, Macfarlane, Gary. J, Rahi, Jugnoo, Stansfeld, Stephen, and Rodgers, Bryan
Abstract: Background: It has been suggested that early life exposures are important determinants of geographical variations in adult diseases. We examined inter-regional migrants in Britain to evaluate the relative importance of early and recent exposures for adult cardiorespiratory risk factors, mental ill-health and sensory function. Methods: A total of 9023 persons born throughout England, Scotland and Wales during 1 week in 1958 were followed periodically through childhood into adulthood. At 44-45 years, height, body mass index (BMI), blood pressure (BP), glycosylated haemoglobin, total and high-density lipoprotein (HDL) cholesterol, triglycerides, fibrinogen, total immunoglobulin E (IgE), one-second forced expiratory volume (FEV1), hearing threshold at 4kHz, visual impairment, symptoms of depression and anxiety, and chronic widespread pain were measured. Analysis of migration between 12 regions included 3125 cohort members who were examined in a region different to their birthplace. Results: Height, BMI, diastolic BP (DBP), FEV1, log-transformed IgE and hearing threshold varied by region among non-migrants (each P < 0.05). Among inter-regional migrants, the spatial associations with current region, independent of birthplace, followed closely the geographical pattern shown among non-migrants for BMI, DBP and FEV1 (each P < 0.001). In contrast, of the 15 outcomes, only adult height was related to region of birth, after adjustment for region of examination (P = 0.002) Conclusions: Although individual disease risk is predicted by early life factors, early exposures do not explain regional variations in cardiovascular and respiratory risk factors among middle-aged adults in Britain. Geographical inequalities in cardiorespiratory health are more strongly related to factors associated with region of examination that influence obesity, BP and ventilatory function.
Published: 2007

44. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., London, Stephanie J., Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., and London, Stephanie J.
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Full Text: View/download PDF

45. Automated diabetic retinopathy image assessment software: diagnostic accuracy and cost-effectiveness compared with human graders

Author: Tufail, Adnan, Rudisill, Caroline, Egan, Catherine, Kapetanakis, Venediktos V., Salas-Vega, Sebastian, Owen, Christopher G., Lee, Aaron, Louw, Vern, Anderson, John, Liew, Gerald, Bolter, Louis, Srinivas, Sowmya, Nittala, Muneeswar, Sadda, SriniVas, Taylor, Paul, Rudnicka, Alicja R., Tufail, Adnan, Rudisill, Caroline, Egan, Catherine, Kapetanakis, Venediktos V., Salas-Vega, Sebastian, Owen, Christopher G., Lee, Aaron, Louw, Vern, Anderson, John, Liew, Gerald, Bolter, Louis, Srinivas, Sowmya, Nittala, Muneeswar, Sadda, SriniVas, Taylor, Paul, and Rudnicka, Alicja R.
Abstract: Objective: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders. Design: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS. Participants: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013. Methods: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration. Main Outcome Measures: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome. Results: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%e95.2%) for any retinopathy, 93.8% (92.9%e94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%e99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %e74.0%) for any retinopathy, 85.0% (83.6%e86.2%) for referable retinopathy, 97.9% (94.9%e99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective. Conclusions: Retmarker and EyeArt

46. An observational study to assess if automated diabetic retinopathy image assessment software can replace one or more steps of manual imaging grading and to determine their cost-effectiveness

Author: Tufail, Adnan, Kapetanakis, Venediktos V, Salas-Vega, Sebastian, Egan, Catherine, Rudisill, Caroline, Owen, Christopher G., Lee, Aaron, Louw, Vern, Anderson, John, Liew, Gerald, Bolter, Louis, Bailey, Clare, Sadda, SriniVas, Taylor, Paul, Rudnicka, Alicja R, Tufail, Adnan, Kapetanakis, Venediktos V, Salas-Vega, Sebastian, Egan, Catherine, Rudisill, Caroline, Owen, Christopher G., Lee, Aaron, Louw, Vern, Anderson, John, Liew, Gerald, Bolter, Louis, Bailey, Clare, Sadda, SriniVas, Taylor, Paul, and Rudnicka, Alicja R
Abstract: Annual diabetic retinopathy screening using digital photographs of the retina assessed by human graders is recognised as the best way to detect vision-threatening disease and reduce visual loss in patients with diabetes mellitus. Vision-threatening disease is referred to hospital eye services for review and possible treatment. With more than 3 million people in England diagnosed with diabetes mellitus, there has been increasing interest in automated systems that detect diabetic retinopathy on digital pictures [so-called automated retinal image analysis systems (ARIASs)] as a way of reducing the need for human graders and the cost of screening. This study compared commercially available ARIASs [IDx-DR (IDx, LLC, Iowa City, IA, USA), iGradingM (version 1.1; originally Medalytix Group Ltd, Manchester, UK, but purchased by Digital Healthcare, Cambridge, UK, at the initiation of the study, purchased in turn by EMIS UK, Leeds, UK, after conclusion of the study), Retmarker (version 0.8.2, Retmarker Ltd, Coimbra, Portugal) and EyeArt (Eyenuk Inc., Woodland Hills, CA, USA)] with human manual grading on retinal photographs from 20,258 consecutive patients seen in a NHS diabetic eye screening programme. IDx, LLC withdrew from the study, citing commercial reasons. The ability of the remaining three ARIASs to correctly identify patients with diabetic retinopathy was compared against trained human graders. Health-economic analyses were carried out to investigate whether or not it would save money if ARIASs replaced trained human graders in different parts of the screening pathway.

47. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., London, Stephanie J., Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., and London, Stephanie J.
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Full Text: View/download PDF

48. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., London, Stephanie J., Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., and London, Stephanie J.
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Full Text: View/download PDF

49. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., London, Stephanie J., Loth, Daan W., Artigas, María Soler, Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Viñuela, Ana, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Pietiläinen, Kirsi H., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Uitterlinden, André G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Gläser, Sven, Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Heliövaara, Markku, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Melén, Erik, Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Dupuis, Josée, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., and London, Stephanie J.
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Database

Publisher

49 results on '"Rudnicka, Alicja R."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources