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ABSTRACT: PURPOSE: To distinguish between contributions to dementia made by homocysteine, folate, B12 and antioxidant micronutrients. METHODS: This is a follow-up study of a sample reported in 2002. Homocysteine was measured at baseline in 201 individuals born in 1921 and without dementia at age 77 years and followed up to age 88 years. Baseline macro- and micronutrient status was estimated from BMI, the MONICA food frequency questionnaire, plasma folate, B12 and, in a subgroup (N = 173), plasma antioxidant micronutrients. Time to dementia onset during follow-up was compared between participants grouped by homocysteine concentration using Cox regression. Model 1 adjusted for age, sex, childhood IQ, education, socioeconomic deprivation, presence of heart disease, hypertension, plasma folate and B12. In model 2 plasma, antioxidants were added to these covariables. RESULTS: During a mean follow-up of about 5 years, there were 39 incident dementia cases among 201 participants. In model 1, being in the highest homocysteine group (>14 μmol/L) was associated with a 234 % increased risk (HR 3.34, 95 % CI 1.16-9.57) of any dementia. After inclusion of plasma antioxidants in model 2, there were 32 incident dementia cases from a subsample (N = 173). Homocysteine >14 μmol was associated with a 272 % increased dementia risk (HR = 3.72, 95 % CI 1.06-13.08). CONCLUSIONS: High homocysteine increases the risk of dementia. The association between tHcy and dementia is independent of plasma folate, B12 and antioxidant micronutrient status.
European Journal of Nutrition 04/2013; · 2.75 Impact Factor
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Neda Jahanshad,
Peter Kochunov,
Emma Sprooten,
René C Mandl,
Thomas E Nichols,
Laura Almassy,
John Blangero,
Rachel M Brouwer,
Joanne E Curran,
Greig I de Zubicaray, [......],
Jessika E Sussmann,
Arthur W Toga,
Joanna M Wardlaw,
Margaret J Wright,
Hilleke E Hulshoff Pol,
Mark E Bastin,
Andrew M McIntosh,
Ian J Deary,
Paul M Thompson,
David C Glahn
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ABSTRACT: The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).
NeuroImage 04/2013; · 5.89 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Ian J Deary,
Jane Elliott,
Sarah E Harris,
Elina Hyppönen,
Mika Kivimaki,
Meena Kumari,
Jane Maddock,
Chris Power, John M Starr,
Diana Kuh,
Ian N M Day
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ABSTRACT: Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled β per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
Journal of Nutrition 03/2013; · 3.92 Impact Factor
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ABSTRACT: BACKGROUND: Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men. METHODS: We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed. RESULTS: Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = -2.12, p < 0.05, partial eta squared 10%). CONCLUSIONS: In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further.
BMC Geriatrics 02/2013; 13(1):20. · 2.34 Impact Factor
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ABSTRACT: Objective: Low health literacy predicts poor health, but the underpinnings of the associations are yet to be understood. This study tested the associations between health literacy and three objective health outcomes in older people and investigated the extent to which general (not health-related) cognition and earlier life-course factors such as childhood cognitive ability, educational level and occupational class accounted for these associations. Method: Participants were 730 community-dwelling older people (350 women; mean age 72.50 years, SD = 0.71). Physical fitness (defined by walk time, lung function, and grip strength), body mass index, and count of natural teeth were used as health outcomes. Rapid Estimate of Adult Literacy in Medicine (REALM), Shortened Test of Functional Health Literacy in Adults (S-TOFHLA), and Newest Vital Sign (NVS) were used to measure health literacy. Age 11 and concurrent general cognitive ability, educational level, and occupational social class were used as covariates. Results: Lower REALM, S-TOFHLA and NVS scores were associated with worse scores on all health outcomes (β = .09 to .17). However, cognitive ability in old age and childhood and educational and occupational levels accounted for the majority of these associations: After adjusting for these covariates, only physical fitness was significantly associated with REALM and S-TOFHLA (β = .06 and .11). Conclusions: Low health literacy was associated with poorer health largely because it reflected general cognitive ability, educational and/or occupational levels. These variables plays some role in health beyond their association with the reading and numeracy skills captured by common health literacy measures. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
Health Psychology 02/2013; · 3.87 Impact Factor
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ABSTRACT: Cytomegalovirus infection has been implicated in cognitive impairment in studies using brief clinical assessments though findings are inconsistent. The association between cytomegalovirus infection, measured as serostatus or a semiquantitative assessment of antibody level, and cognitive abilities in a sample of older adults was examined. Cytomegalovirus status was assessed at a mean age of 70 years in 1061 participants of the Lothian Birth Cohort 1936. Cognitive ability scores were available for general cognitive ability, processing speed, memory, and vocabulary. Background demographic and environmental factors included father's social class, years of education, childhood cognitive ability, overcrowding in childhood, and access to indoor toilet facilities. Cytomegalovirus seropositive individuals had lower cognitive ability at age 70: mean IQ was 99.1 (SD, 15.1) versus 102.4 (SD, 13.1) in seronegative individuals (t = 3.65; p < 0.001). The likelihood of contracting cytomegalovirus infection by age 70 was predicted by a number of demographic and environmental factors and, after accounting for these, cytomegalovirus infection (considered as serostatus) was not cognitively detrimental. Within cytomegalovirus seropositive individuals, however, higher cytomegalovirus antibody levels were associated with lower general cognitive ability.
Neurobiology of aging 02/2013; · 5.94 Impact Factor
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Andrew M McIntosh,
Alan Gow,
Michelle Luciano,
Gail Davies,
David C Liewald,
Sarah E Harris,
Janie Corley,
Jeremy Hall, John M Starr,
David J Porteous,
Albert Tenesa,
Peter M Visscher,
Ian J Deary
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ABSTRACT: BACKGROUND: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS. METHODS: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS. RESULTS: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis. CONCLUSIONS: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.
Biological psychiatry 02/2013; · 8.93 Impact Factor
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Eleonora Porcu,
Marco Medici,
Giorgio Pistis,
Claudia B Volpato,
Scott G Wilson,
Anne R Cappola,
Steffan D Bos,
Joris Deelen,
Martin den Heijer,
Rachel M Freathy, [......],
Theo J Visser,
Bruce H R Wolffenbuttel,
Ingrid Meulenbelt,
Jerome I Rotter,
Tim D Spector,
Andrew A Hicks,
Daniela Toniolo,
Serena Sanna,
Robin P Peeters,
Silvia Naitza
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ABSTRACT: Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.
PLoS Genetics 02/2013; 9(2):e1003266. · 8.69 Impact Factor
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Rebecca Hardy,
Rachel Cooper,
Avan Aihie Sayer,
Yoav Ben-Shlomo,
Cyrus Cooper,
Ian J Deary,
Panayotes Demakakos,
John Gallacher,
Richard M Martin,
Geraldine McNeill, John M Starr,
Andrew Steptoe,
Holly Syddall,
Diana Kuh
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ABSTRACT: To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
PLoS ONE 01/2013; 8(2):e56483. · 4.09 Impact Factor
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ABSTRACT: Recent reports suggest a causal relationship between education and IQ, which has implications for cognitive development and aging-education may improve cognitive reserve. In two longitudinal cohorts, we tested the association between education and lifetime cognitive change. We then tested whether education is linked to improved scores on processing-speed variables such as reaction time, which are associated with both IQ and longevity. Controlling for childhood IQ score, we found that education was positively associated with IQ at ages 79 (Sample 1) and 70 (Sample 2), and more strongly for participants with lower initial IQ scores. Education, however, showed no significant association with processing speed, measured at ages 83 and 70. Increased education may enhance important later life cognitive capacities, but does not appear to improve more fundamental aspects of cognitive processing. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Psychology and Aging 12/2012; · 2.73 Impact Factor
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Donald M Lyall,
Lorna M Lopez,
Mark E Bastin,
Susana Muñoz Maniega,
Lars Penke,
Maria Del C Valdés Hernández,
Natalie A Royle, John M Starr,
David J Porteous,
Joanna M Wardlaw,
Ian J Deary
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ABSTRACT: The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686-765, and for neuroimaging variables was N = 488-587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.
Behavior Genetics 12/2012; · 2.52 Impact Factor
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Pim van der Harst,
Weihua Zhang,
Irene Mateo Leach,
Augusto Rendon,
Niek Verweij,
Joban Sehmi,
Dirk S Paul,
Ulrich Elling,
Hooman Allayee,
Xinzhong Li, [......],
Manuel A Ferreira,
Serena Sanna,
Manuela Uda,
Andrew A Hicks,
Josef Martin Penninger,
Christian Gieger,
Jaspal S Kooner,
Willem H Ouwehand,
Nicole Soranzo,
John C Chambers
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ABSTRACT: Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Nature 12/2012; · 36.28 Impact Factor
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ABSTRACT: Objectives
Studies have reported associations between the five-factor model's personality traits and inflammation markers interleukin-6 (IL-6) and C-reactive protein (CRP). Findings, however, have been inconsistent. This study investigates these associations in individuals who ranged in age from approximately 70 to 73 years.Methods
Participants were from the Lothian Birth Cohort 1936 (n = 818). Acute-phase proteins-CRP and fibrinogen-were measured at ages approximately 70 years (first wave) and 73 years (second wave), and the inflammatory cytokine IL-6 was measured at age 73 years. Personality traits were measured at age 70 years using two instruments, the International Personality Item Pool and the NEO Five-Factor Inventory.ResultsLower International Personality Item Pool conscientiousness was cross-sectionally associated with elevated CRP, such that 1 standard deviation higher conscientiousness was associated with 22% lower odds of having a CRP level greater than 3 mg/l (odds ratio = 0.78; 95% confidence interval = 0.67-0.91). NEO Five-Factor Inventory openness was negatively associated with CRP (odds ratio = 0.79; 95% confidence interval = 0.67-0.94) and IL-6 (β = -.08, p = .045) at age 73 years; these associations were attenuated by 26% and 63%, respectively, after adjusting for social background and prior cognitive ability. Body mass index mediated some (14%-18%) of the conscientiousness-inflammation association, whereas common health behaviors such as smoking, alcohol consumption, and physical activity did not significantly mediate the personality trait-inflammatory marker association.Conclusions
The findings add some support to accumulating evidence for low conscientiousness being linked to higher levels of inflammation and poorer general health.
Psychosomatic Medicine 11/2012; · 3.97 Impact Factor
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ABSTRACT: OBJECTIVES: Increased participation in leisure and physical activities may be cognitively protective. Whether activity might protect the integrity of the brain's white matter, or reduce atrophy and white matter lesion (WML) load, was examined in the Lothian Birth Cohort 1936 (n = 691), a longitudinal study of aging. METHODS: Associations are presented between self-reported leisure and physical activity at age 70 years and structural brain biomarkers at 73 years. For white matter integrity, principal components analysis of 12 major tracts produced general factors for fractional anisotropy (FA) and mean diffusivity. Atrophy, gray and normal-appearing white matter (NAWM) volumes, and WML load were assessed using computational image processing methods; atrophy and WML were also assessed visually. RESULTS: A higher level of physical activity was associated with higher FA, larger gray and NAWM volumes, less atrophy, and lower WML load. The physical activity associations with atrophy, gray matter, and WML remained significant after adjustment for covariates, including age, social class, and health status. For example, physical activity (standardized β = -0.09, nonstandardized β = -0.09, p = 0.029) and stroke (standardized β = 0.18, nonstandardized β = 0.69, p = 0.003) each had an independent effect on rated WML load. Leisure activity was associated with NAWM volume, but was nonsignificant after including covariates. CONCLUSIONS: In this large, narrow-age sample of adults in their 70s, physical activity was associated with less atrophy and WML. Its role as a potential neuroprotective factor is supported; however, the direction of causation is unclear from this observational study.
Neurology 10/2012; 79(17):1802-1808. · 8.31 Impact Factor
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ABSTRACT: BACKGROUND: Physical, emotional, and psychosocial wellbeing are important domains of function. The aims of this study were to explore the existence of separable groups among 70-year olds with scores representing physical function, perceived quality of life, and emotional wellbeing, and to characterise any resulting groups using demographic, personality, cognition, health and lifestyle variables. METHODS: We used latent class analysis (LCA) to identify possible groups. RESULTS: Results suggested there were 5 groups. These included High (n = 515, 47.2% of the sample), Average (n = 417, 38.3%), and Poor Wellbeing (n = 37, 3.4%) groups. The two other groups had contrasting patterns of wellbeing: one group scored relatively well on physical function, but low on emotional wellbeing (Good Fitness/ Low Spirits, n = 60, 5.5%), whereas the other group showed low physical function but relatively well emotional wellbeing (Low Fitness/Good Spirits, n = 62, 5.7%). Salient characteristics that distinguished all the groups included smoking and drinking behaviours, personality, and illness. CONCLUSIONS: Despite there being some evidence of these groups, the results also support a largely one-dimensional construct of wellbeing in old age---for the domains assessed here---though with some evidence that some individuals have uneven profiles.
BMC Geriatrics 10/2012; 12(1):64. · 2.34 Impact Factor
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Tamuno Alfred,
Yoav Ben-Shlomo,
Rachel Cooper,
Rebecca Hardy,
Cyrus Cooper,
Ian J Deary,
David Gunnell,
Sarah E Harris,
Meena Kumari,
Richard M Martin,
Avan Aihie Sayer, John M Starr,
Diana Kuh,
Ian N M Day
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ABSTRACT: BACKGROUND: Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability. METHODS: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90+ years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance. RESULTS: Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p=0.05, n=11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures. CONCLUSION: Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
Bone 10/2012; · 4.02 Impact Factor
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ABSTRACT: The body that organized and published the results of the Scottish Mental Surveys of 1932 and 1947 (SMS1932 and SMS1947) was the Scottish Council for Research in Education (SCRE; Craigie, 1972). For most of its history, the SCRE was an autonomous research body, not part of any university, college, or other educational institution. Since 2002, it has been known as the SCRE Centre at the University of Glasgow (Scotland, United Kingdom). Researchers at the SCRE retained the raw data from the SMS1932 and SMS1947 and, in 2007, deposited them in the archives of the University of Glasgow. The SCRE originally published the results of the surveys. Most of the individuals who planned, executed, and wrote up the results of the SMS1932 and SMS1947 were not employed by or primarily affiliated with the SCRE. The SCRE provided the rallying point for the collaboration; it was the nodal point in a network. The salaried staff of the SCRE between its institution in 1928 and 1946 comprised just an honorary director, a secretarial assistant, and a clerkess (SCRE, 1953a). The SCRE's wide representation was one of the factors in its success. Experts volunteered assistance with studies. For example, very senior academics, such as Professor Godfrey H. Thomson (1969), undertook huge design and analytic tasks for the SCRE's research projects. Education authorities gave funding and permitted studies to take place in their geographic areas. Directors of education helped with the distribution of tests for studies. The Educational Institute of Scotland (EIS), the body representing teachers, provided the SCRE's regular funding, and the EIS's members—the teachers—gathered data and administered and scored thousands of tests. All of this was helped by the fact that Scotland was one of the first countries to have a large proportion of teachers with degrees, and its universities were active in teaching educational research. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
10/2012;
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Nora Franceschini,
Frank J A van Rooij,
Bram P Prins,
Mary F Feitosa,
Mahir Karakas,
John H Eckfeldt,
Aaron R Folsom,
Jeffrey Kopp,
Ahmad Vaez,
Jeanette S Andrews, [......],
Alan F Wright,
Qingyu Wu,
Yongmei Liu,
Nancy S Jenny,
Kari E North,
Janine F Felix,
Behrooz Z Alizadeh,
L Adrienne Cupples,
John R B Perry,
Andrew P Morris
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ABSTRACT: Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10(-8)) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations. Other loci associated with serum albumin harbor genes related to ribosome function, protein translation, and proteasomal degradation, whereas those associated with serum total protein include genes related to immune function. Our results highlight the advantages of transethnic meta-analysis for the discovery and fine mapping of complex trait loci and have provided initial insights into the underlying genetic architecture of serum protein concentrations and their association with human disease.
The American Journal of Human Genetics 09/2012; 91(4):744-753. · 10.60 Impact Factor
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ABSTRACT: The current study investigated the associations between thyroid stimulating hormone (TSH), free thyroxine (T(4)) and cognitive ability (general ability, memory and processing speed), in a large age homogenous sample (n=659) of generally healthy euthyroid older adults. Associations were considered both at baseline (mean age wave 1=69.5 years; SD=0.8 years) and approximately 3 years later (mean age wave 2=72.5 years; SD=0.7 years). Results indicated mean level decreases across waves in both TSH (t=10.99, p<0.001) and T(4) (t=34.55, p<0.001). There were no significant associations between TSH and T(4) with any of the cognitive variables at either wave. There was no suggestion of non-linear associations. The lack of associations supports suggestions that the effects of thyroid hormones on cognition may be restricted to older individuals above a given threshold, and/or those with levels of thyroid hormones within the range defining clinical thyroid disorder.
Psychoneuroendocrinology 09/2012; · 5.81 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVE:To investigate the relationship between retinal vessel morphology (branching coefficient, bifurcation angle, and fractal analysis) and retinal nerve fiber layer (RNFL) thickness in an elderly population. PATIENTS AND METHODS:One hundred and one participants from the Lothian Birth Cohort 1936 (population of people all born in 1936) were studied. RNFL thickness measurements (using optical coherence tomography [OCT]) and digital retinal photographs were collected. The retinal images were analyzed using custom-designed software called the Vascular Assessment and Measurement Platform for Images of the Retina. RESULTS:Greater deviation from the optimal arteriolar branching coefficient was associated with greater RNFL thickness (r = 0.249, P = .028). There was no significant association between RNFL thickness and the other retinal vessel morphology parameters. CONCLUSION:RNFL thickness increased significantly with suboptimality of arteriole branching coefficient. These findings cannot be explained by our current understanding of OCT. OCT-based biomarker metrics require further study to better define retinal neurovascular imaging and anatomy.
Ophthalmic Surgery Lasers and Imaging 08/2012; · 0.62 Impact Factor
