[Show abstract][Hide abstract] ABSTRACT: We previously reported an association between high bone mass (HBM) and a bone-forming phenotype of radiographic hip osteoarthritis (OA). As knee and hip OA have distinct risk factors, in this study we aimed to determine (i) whether HBM is also associated with knee OA, and (ii) whether the HBM knee OA phenotype demonstrates a similar pattern of radiographic features to that observed at the hip.HBM cases (defined by DXA BMD Z-scores) from the UK-based HBM study were compared with unaffected family controls and general population controls from the Chingford and Hertfordshire cohort studies. A single blinded observer graded AP weight-bearing knee radiographs for features of OA (Kellgren–Lawrence score, osteophytes, joint space narrowing (JSN), sclerosis) using an atlas. Analyses used logistic regression, adjusting a priori for age and gender, and additionally for BMI as a potential mediator of the HBM–OA association, using Stata v12.609 HBM knees in 311 cases (mean age 60.8 years, 74% female) and 1937 control knees in 991 controls (63.4 years, 81% female) were analysed. The prevalence of radiographic knee OA, defined as Kellgren–Lawrence grade ≥ 2, was increased in cases (31.5% vs. 20.9%), with age and gender adjusted OR [95% CI] 2.38 [1.81, 3.14], p < 0.001. The association between HBM and osteophytosis was stronger than that for JSN, both before and after adjustment for BMI which attenuated the ORs for knee OA and osteophytes in cases vs. controls by approximately 50%.Our findings support a positive association between HBM and knee OA. This association was strongest for osteophytes, suggesting HBM confers a general predisposition to a subtype of OA characterised by increased bone formation.
[Show abstract][Hide abstract] ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls.
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 06/2014;
[Show abstract][Hide abstract] ABSTRACT: Background: Peer interaction plays an important role in the development of social competence, and problematic childhood peer relationships often precede later maladjusted behaviour. Some links between early peer rejection and later maladaptive functioning however might be mediated through an underlying pathology. This includes impairments in social interaction skills, which are characteristic and heritable symptoms of the autistic dimension including Autism Spectrum disorders (ASD).
Objectives: Our study i) aimed to investigate genetic influences contributing to impaired peer relationships during childhood and adolescence, and ii) to identify population-based single SNP signals, which also contribute to risk for ASD.
Methods: Heritability was estimated using ≤7366 UK twin pairs (Twins Early Development Study, TEDS) with parent-report on peer problems at 4, 7, 9 and 11 years. A genome-wide analysis was conducted within N≤6000 children from a UK birth-cohort (Avon Longitudinal Study of Parents and children, ALSPAC) with parent-report on peer problems at 4, 7, 8, 10, 12, 13 and 17 years. Association signals were followed-up within independent children from TEDS (N≤2837) and were also investigated in the Autism Genetic Research Exchange (AGRE) sample (793 ASD pedigrees) and the Autism Case-Control cohort (ACC, 1204 ASD subjects, 6491 control subjects).
Results: Problematic peer relationships are substantially heritable throughout early/middle childhood (h2=0.60-0.71). During this developmental period however, there might be only few measurable common additive genetic effects (DNA-based h2≤0.12). During later adolescence by contrast the proportion of measurable common additive genetic effects is increasing (DNA-based h2=0.14-0.27). Two population-based signals in ALSPAC (rs6451614 at 5p13.1 near GHR, P17years=9.6x10-6, rs7873232 at 9p24.2 near GLIS3 and RFX3, P13years=7.3x10-6) were identified during later adolescence (out of 50 independent signals with P<10-5 across all time-points) and showed evidence for replication in AGRE (rs6451614 P=0.00058, rs7873232 P=0.0030), but not the ACC (rs1858136, proxy for rs6451614, r2=0.88, P=0.69; rs7873232 P=0.99). No comparable effect was observed within TEDS children spanning a younger age-range. Longitudinal modelling confirmed that genetic effects at both rs6451614 and rs7873232 varied across development, and that the underlying associations are complex.
Conclusions: Common genetic effects contribute to variation in problematic peer relationships, however the influence of measurable common additive genetic effect is strongest in later adolescence. Overlaps with the autistic continuum might be present, but many more samples might be required to reliably identify single associations.
2014 International Meeting for Autism Research; 05/2014
[Show abstract][Hide abstract] ABSTRACT: Background: Maternal smoking during pregnancy has been discussed as a potential risk factor for the increase of autistic symptoms in children, though findings have been inconsistent. It is possible however that maternal smoking might only elevate the expression of autistic symptoms in genetically susceptible individuals, and thus GxE may conceal the true underlying relationship between risk factor and behavioural outcome.
Objectives: We aimed to identify genetic moderators of the risk effect of maternal smoking on the expression of autism-related social communication difficulties during childhood and adolescence using a genome-wide GxE analysis.
Methods: We performed a 2-stage genome-wide GxE analysis with respect to social communication problems as captured by the Social and Communication Disorders Checklist (SCDC). Measurements were assessed in a large UK population-based birth cohort at 8, 11, 14 and 17 years of age (Avon Longitudinal Study of Parents and Children, N ≤ 5539). During the first stage, we performed a genome-wide screen for differences in phenotypic variance per genotype (Levene’s test) using 2.5 million imputed or genotyped SNPs and investigating each time-point individually. This identified a set of variants, which is likely to be involved in interactions. During the second-stage, we investigated all independent signals with respect to maternal smoking during the first trimester (adjusted for child’s age and sex), performing a joint likelihood ratio test for both G+GxE and E+GxE respectively using negative binomial regression.
Results: Maternal smoking during the first trimester was identified as a strong predictor of increased autistic traits at 8 years of age (β=0.23(0.05), measured in log-counts of social-communication problems, P=4.4x10-7), but the risk effect declined during the course of development. During stage one of our GxE screen, we identified 132 independent offspring SNPs (Levene-P<10-5, LD based clumping: r2=0.2, ±500kb, in addition to all SNPs in known ASD candidate regions with P<10-4) across all 4 time-points, which are likely to be involved in interaction effects. The strongest E+GxE signal (Levene-P=5.2x10-5,PGxE=0.00016 (PGxE_adj=0.021), PE+GxE=1.7x10-9) was observed for variation in the ASD-candidate gene A2BP1 (alias RBFOX1) and was associated with social-communication problems at 8 years of age. There was no evidence for a genetic main effect (PG=0.96). Stratification by genotype, showed that the risk effect of maternal smoking was only present in homozygote carriers of the major (risk) allele (0 risk allele: β(smoking) = -0.23(0.20), P =0.27, 1 risk allele: β(smoking) = 0.057(0.084), P=0.50, 2 risk alleles: β(smoking)=0.35(0.057), P=5.8x10-10). The interaction was attenuated with progressive age due to the decline in risk effect of smoking. We found no joint G+GxE effect (P<10-5), which provided more evidence for association than G alone. Replication of the interaction signal is currently being sought within independent cohorts.
Conclusions: Our variance-based genome-wide screen identified a small set of SNPs that are probably involved in interactions either with environmental or other SNP variation. We identified one GxE interaction effect, which, if replicated, might indicate that offspring of some smoking mothers are at particularly high risk for social-communication problems in childhood and adolescence.
2014 International Meeting for Autism Research; 05/2014
[Show abstract][Hide abstract] ABSTRACT: Objective
Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls.
HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and BMI.
530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs. 13.6%), with adjusted OR [95% CI] 1.52 [1.09,2.11], p=0.013. Osteophytes (OR 2.12 [1.61,2.79], p<0.001) and subchondral sclerosis (OR 2.78 [1.49,5.18], p=0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing was seen (OR 0.97 [0.72,1.33], p=0.869).
An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype.
Osteoarthritis and Cartilage 04/2014; · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:Few studies have prospectively investigated whether early-life exposures are associated with pre-adolescent eating attitudes.Objective:The objective of this study is to prospectively investigate associations of parental smoking, alcohol use, marital status, measures of maternal satisfaction, self-reported parental body mass index (BMI) and clinically measured childhood BMI, assessed between birth and 6.5 years, with problematic eating attitudes at 11.5 years.Methods:Observational cohort analysis nested within the Promotion of Breastfeeding Intervention Trial, a cluster-randomised trial conducted in 31 maternity hospitals and affiliated polyclinics in Belarus. Our primary outcome was a Children's Eating Attitudes Test (ChEAT) score 22.5 (85th percentile), an indicator of problematic eating attitudes. We employed multivariable mixed logistic regression models, which allow inference at the individual level. We also performed instrumental variable (IV) analysis using parents' BMIs as instruments for the child's BMI, to assess whether associations could be explained by residual confounding or reverse causation.Subjects:Of the 17 046 infants enrolled between 1996 and 1997 across Belarus, 13 751 (80.7%) completed the ChEAT test at 11.5 years.Results:In fully adjusted models, overweight children at age 6.5 years had a 2.14-fold (95% confidence interval (CI): 1.82, 2.52) increased odds of having ChEAT scores 85th percentile at age 11.5 years, and those who were obese had a 3.89-fold (95% CI: 2.95, 5.14) increased odds compared with normal-weight children. Children of mothers or fathers who were themselves overweight or obese were more likely to score 85th percentile (P for trend 0.001). IV analysis was consistent with a child's BMI causally affecting future eating attitudes. There was little evidence that parental smoking, alcohol use, or marital status or maternal satisfaction were associated with eating attitudes.Conclusion:In our large, prospective cohort in Belarus, both parental and childhood overweight and obesity at 6.5 years were associated with pre-adolescent problematic eating attitudes 5 years later.
[Show abstract][Hide abstract] ABSTRACT: Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common. Method Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961-1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory. RESULTS: Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11-0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07-0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09-0.40) but father smoking was not (β = 0.02, 95% CI -0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03-0.49) or did not smoke (β = 0.30, 95% CI 0.04-0.57). By number of cigarettes, associations with hyperactivity were present for 10-19 and 20+ cigarettes per day among mothers. CONCLUSIONS: In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.
Psychological Medicine 05/2013; · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.Molecular Psychiatry advance online publication, 29 January 2013; doi:10.1038/mp.2012.184.
[Show abstract][Hide abstract] ABSTRACT: Background: Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems. Aim: We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect. Methods: This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire. Results: In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05-1.43; ALSPAC: OR 1.33, 95% CI 1.19-1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06-1.46; ALSPAC: OR 1.32, 95% CI 1.19-1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00-1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child. Conclusions: The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.
Journal of Child Psychology and Psychiatry 12/2012; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence.Method
In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.09, p=0.002] but there was no association with depression (p=0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97-1.09, p=0.34) or depression (OR 1.02, 95% CI 0.95-1.09, p=0.62) among smokers. CONCLUSIONS: As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.
Psychological Medicine 06/2012; · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)-maternal education and family income-and maternal and infant health outcomes between ALSPAC and Pelotas cohorts.
Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts.
An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts.
Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.
Journal of epidemiology and community health 02/2012; 66(2):127-35. · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Taller adults have a reduced risk of cardiovascular disease, and there is some evidence that pre-adolescent exposures, indexed by leg length, underlie this association. Associations with other aspects of skeletal size in childhood have not previously been investigated.
We have examined associations of cardiovascular mortality and morbidity with childhood height, shoulder breadth, leg, trunk and foot length using a cohort of children whose families participated in a 1937-9 survey of diet and health followed up for 59 years.
Altogether 2642 traced participants had at least one anthropometric measurement; a subsample (n=1043), completed the Rose angina questionnaire and provided information about doctor-diagnosed ischaemic heart disease (IHD) in 1997-8. Childhood stature was weakly inversely associated with cardiovascular mortality, and leg length was the component with the strongest associations. There was evidence from secondary analyses that childhood anthropometric measurements were inversely related to early (age <65 years) rather than late cardiovascular mortality. Childhood stature was inversely associated with self-reported IHD and associations with leg length were strongest. Associations were somewhat attenuated in models including terms for having been breastfed and socioeconomic position.
Pre-adult exposures are more strongly associated with cardiovascular morbidity than mortality, and they affect premature cardiovascular mortality more than later mortality.
Journal of epidemiology and community health 01/2012; 66(1):18-23. · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As low folate status has been implicated in depression, high folate intake, in the form of supplements, during pregnancy might offer protection against depression during pregnancy and postpartum.
We examined the association between change in self-reported depressive symptoms (Edinburgh Postnatal Depression Scale) at different timepoints during and following pregnancy and self-reported folic acid supplementation during pregnancy in a prospective cohort of 6809 pregnant women. We also tested whether there was a main effect of methylenetetrahydrofolate reductase (MTHFR) C677T genotype (which influences folate metabolism and intracellular levels of folate metabolites and homocysteine) on change in depression scores, and carried out our analysis of folic acid supplementation and depression stratifying by genotype.
We found no strong evidence that folic acid supplementation reduced the risk of depression during pregnancy and up to 8 months after pregnancy. However, we did find evidence to suggest that folic acid supplements during pregnancy protected against depression 21 months postpartum, and that this effect was more pronounced in those with the MTHFR C677T TT genotype (change in depression score from 8 months to 21 months postpartum among TT individuals was 0.66 (95% CI=0.31-1.01) among those not taking supplements, compared with -1.02 (95% CI=-2.22-0.18) among those taking supplements at 18 weeks pregnancy, P(difference)=0.01).
Low folate is unlikely to be an important risk factor for depression during pregnancy and for postpartum depression, but may be a risk factor for depression outside of pregnancy, especially among women with the MTHFR C677T TT genotype.
European journal of clinical nutrition 07/2011; 66(1):97-103. · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIMS/PURPOSE: To determine the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in men aged 65-83 years living in the Speedwell region of Bristol, United Kingdom and identify modifiable risk factors.
A total of 2348 men recruited to the Speedwell prospective cohort study in 1979 were followed up in 1997 with an eye questionnaire and had retinal photographs that were assessed using the International Classification System for ARM.
In all, 934 men (66.8% response rate) attended with a mean of 17.9 years (15.3-20.6 years) follow-up. Early ARM (grades 2-3) was found in 9.2% (95% confidence interval (CI) 7.4%, 11.4%) and late age-related maculopathy (grade 4, AMD) in 0.5% (95% CI 0.2%, 1.2%). The risk of ARM (grades 2-4) was increased with raised C-reactive protein and consumption of lard and solid fats, whereas triglyceride levels were associated with a lower risk. The latter were confirmed in multivariable analyses and in addition, haemodynamic measures also predicted risk (eg mean arterial pressure odds ratio (OR) per z-score 1.37, 95% CI 1.04, 1.79).
In a representative cohort of men aged 65-83 from Bristol, United Kingdom, many had macular changes that put them at higher risk of developing AMD. Various modifiable exposures were associated with an increased risk ARM/AMD. Opportunities for screening and undertaking secondary prevention interventions need to be explored to prevent progression of the disease and blindness.