Biology subjects

Pedersen, N. L.

Publications and source records attributed to Pedersen, N. L..

6 recordsLinked to original sources

bioRxiv2017

The Anorexia Nervosa Genetics Initiative: Overview and Methods

BackgroundGenetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.\n\nMethodsANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.\n\nResultsBlood samples and clinical information were collected from 13,364 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.\n\nConclusionsOur multipronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.gov NCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

genetics↗

bioRxiv2017

A frailty index for UK Biobank participants

BackgroundFrailty indices (FIs) measure variation in health between aging individuals. Researching FIs in resources with large-scale genetic and phenotypic data will provide insights into the causes and consequences of frailty. Thus, we aimed to develop an FI using UK Biobank data, a cohort study of 500,000 middle-aged and older adults.\n\nMethodsAn FI was calculated using 49 self-reported questionnaire items on traits covering health, presence of diseases and disabilities, and mental wellbeing, according to standard protocol. We used multiple imputation to derive FI values for the entire eligible sample in the presence of missing item data (N =500,336). To validate the measure, we assessed associations of the FI with age, sex, and risk of all-cause mortality (follow-up [≤] 9.7 years) using linear and Cox proportional hazards regression models.\n\nResultsMean FI in the cohort was 0.125 (standard deviation = 0.075), and there was a curvilinear trend towards higher values in older participants. FI values were also marginally higher on average in women than men. In survival models, 10% higher baseline frailty (i.e. a 0.1 FI increment) was associated with higher risk of death (hazard ratio (HR) = 1.65; 95% confidence interval: 1.62, 1.68). Associations were stronger in younger participants than in old, and in men compared to women (HRs: 1.72 vs. 1.56, respectively).\n\nConclusionsThe FI is a valid measure of frailty in UK Biobank. The cohorts data are open-access for researchers to use, and we provide script for deriving this tool to facilitate future studies on frailty.

epidemiology↗

bioRxiv2017

Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins

Age-related changes in DNA methylation have been observed in many cross-sectional studies, but longitudinal evidence is still very limited. Here, we aimed to characterize longitudinal age-related methylation patterns (Illumina HumanMethylation450 array) using 1011 blood samples collected from 385 old Swedish twins (mean age of 69 at baseline) up to five times over 20 years. We identified 1316 age-associated methylation sites (p<1.3x10-7) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in PIVUS (p<3.9x10-5) and 594 were replicated in LBC (p<5.1x10-5). Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other unannotated transcription factor binding sites. We further investigated genetic influences on methylation (methylation quantitative trait loci) and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased over time, where monozygotic twins had smaller intra-pair differences than dizygotic twins. We show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. Moreover, the changes are under genetic influence, although this effect is independent of age. In addition, inter-individual methylation variations increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

genetics↗

bioRxiv2017

The frailty index is associated with the need for care in an aging Swedish population

BackgroundThe Rockwood frailty index (FI) has proven a valid predictor of mortality, institutionalization and requirement for health services. However, little is known about the relationship between the FI and the need for care - an indication of dependency. To this end, we ascertained the associations between the FI and the need for current and future care.\n\nMethodsA Rockwood-based FI was tested for association with the current need for care and care needs in the future during a 23-year follow-up in the Swedish Adoption/Twin Study of Aging (n=1477; 623 men, 854 women; aged 29-95 years at baseline). Need for care was defined as receiving help at least once a week in daily routines. Age, sex, education, living alone, smoking status and body mass index were considered as covariates.\n\nResultsThe FI was independently associated with current need for care (OR=1.27 for accumulation of one deficit, 95%CI 1.20-1.34) and future need for care (HR=1.12 for accumulation of one deficit, 95%CI 1.08-1.15). Co-twin control analyses confirmed the results; the pair member currently needing care had higher median FI levels compared to their co-twin not needing care, and the pair member having higher baseline FI had shorter median time to the onset of future care need compared to their co-twin with lower FI.\n\nConclusionsThe FI is a determinant of current care needs and predictive of care needs in the future. The FI may thus represent a risk indicator for dependency and offer an amenable target for preventive measures.

epidemiology↗

bioRxiv2017

Frailty index as a predictor of all-cause and cause-specific mortality in a Swedish population-based cohort

BackgroundFrailty is a complex manifestation of aging and associated with increased risk of mortality and poor health outcomes. Younger individuals (under 65 years) typically have low levels of frailty and are less-studied in this respect. Also, the relationship between the Rockwood frailty index (FI) and cause-specific mortality in community settings is understudied.\n\nMethodsWe created and validated a 42-item Rockwood-based FI in The Swedish Adoption/Twin Study of Aging (n=1477; 623 men, 854 women; aged 29-95 years) and analyzed its association with all-cause and cause-specific mortality in up to 30-years of follow-up. Deaths due to cardiovascular disease (CVD), cancer, dementia and other causes were considered as competing risks.\n\nResultsOur FI demonstrated construct validity as its associations with age, sex and mortality were similar to the existing literature. The FI was independently associated with increased risk for all-cause mortality in younger (<65 years; HR per increase in one deficit 1.11, 95%CI 1.07-1.17) and older ([≥]65 years; HR 1.07, 95%CI 1.04-1.10) women and in younger men (HR 1.05, 95%CI 1.01-1.10). In cause-specific mortality analysis, the FI was strongly predictive of CVD mortality in women (HR per increase in one deficit 1.13, 95%CI 1.09-1.17), whereas in men the risk was restricted to deaths from other causes (HR 1.07, 95%CI 1.01-1.13).\n\nConclusionsThe FI showed good predictive value for all-cause mortality especially in the younger group. The FI predicted CVD mortality risk in women, whereas in men it captured vulnerability to death from various causes.

epidemiology↗

bioRxiv2017

An epigenome-wide association study of educational attainment (n = 10,767)

The epigenome has been shown to be influenced by biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications--in our case, CpG methylation--and educational attainment (EA), a biologically distal environmental factor that is arguably among of the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 individuals. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the sample to never-smokers. These two are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes--polygenic methylation score and epigenetic-clock analyses--both suggest small associations with EA. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

genetics↗