Birgir Hrafnkelsson

An Icelandic example of the impact of population structure on association studies

The impact of population structure on association studies undertaken to identify genetic variants underlying common human diseases is an issue of growing interest. Spurious associations of alleles with disease phenotypes may be obtained or true associations overlooked when allele frequencies differ notably among subpopulations that are not represented equally among cases and controls. Population structure influences even carefully designed studies and can affect the validity of association results. Most study designs address this problem by sampling cases and controls from groups that share the same nationality or self-reported ethnic background, with the implicit assumption that no substructure exists within such groups. We examined population structure in the Icelandic gene pool using extensive genealogical and genetic data. Our results indicate that sampling strategies need to take account of substructure even in a relatively homogenous genetic isolate. This will probably be even more important in larger populations.

A Populationwide Coalescent Analysis of Icelandic Matrilineal and Patrilineal Genealogies: Evidence for a Faster Evolutionary Rate of mtDNA Lineages than Y Chromosomes

Historical inferences from genetic data increasingly depend on assumptions about the genealogical process that shapes the frequencies of alleles over time. Yet little is known about the structure of human genealogies over long periods of time and how they depart from expectations of standard demographic models, such as that attributed to Wright and Fisher. To obtain such information and to examine the recent evolutionary history of mtDNA and Y-chromosome haplotypes in the Icelandic gene pool, we traced the matrilineal and patrilineal ancestry of all 131,060 Icelanders born after 1972 back to two cohorts of ancestors, one born between 1848 and 1892 and the other between 1798 and 1742. This populationwide coalescent analysis of Icelandic genealogies revealed highly positively skewed distributions of descendants to ancestors, with the vast majority of potential ancestors contributing one or no descendants and a minority of ancestors contributing large numbers of descendants. The expansion and loss of matrilines and patrilines has caused considerable fluctuation in the frequencies of mtDNA and Y-chromosome haplotypes, despite a rapid population expansion in Iceland during the past 300 years. Contrary to a widespread assumption, the rate of evolution caused by this lineage-sorting process was markedly faster in matrilines (mtDNA) than in patrilines (Y chromosomes). The primary cause is a 10% shorter matrilineal generation interval. Variance in the number of offspring produced within each generation was not an important differentiating factor. We observed an intergenerational correlation in offspring number and in the length of generation intervals in the matrilineal and patrilineal genealogies, which was stronger in matrilines and thus contributes to their faster evolutionary rate. These findings may have implications for coalescent date estimates based on mtDNA and Y chromosomes.

Psychotropic Drug Use among Icelandic Children: A Nationwide Population-Based Study

OBJECTIVE The aim of this study was to investigate psychotropic drug use among children in Iceland between 2003 and 2007. METHODS A nationwide population-based drug use study covering the total pediatric population (ages 0-17) in Iceland. Information was obtained from the National Medicines Registry to calculate prevalence of use by year and psychotropic drug group; incidence by year, psychotropic drug group, childs age and sex, and medical specialty of prescriber; the most commonly used psychotropic chemical substances, off-label and unlicensed use and concomitant psychotropic drug use. RESULTS The overall prevalence of psychotropic drug use was 48.7 per 1000 Icelandic children in 2007. Stimulants and antidepressants increased in prevalence from 2003 to 2007 and were the two most prevalent psychotropic drug groups, respectively, 28.4 and 23.4 per 1000 children in 2007. A statistically significant trend of declining prevalence (p = 0.00013) and incidence (p = 0.0018) of antidepressant use occurred during the study period. Out of 21,986 psychotropic drugs dispensed in 2007, 25.4% were used off-label. CONCLUSIONS With reference to reports from other European countries, the results indicate extensive psychotropic drug use among children in Iceland between 2003 and 2007. Further scrutiny is needed to assess the rationale behind this widespread use.

Hierarchical modeling of count data with application to nuclear fall-out

We propose a method for a Bayesian hierarchical analysis of count data that are observed at irregular locations in a bounded domain of R2. We model the data as having been observed on a fine regular lattice, where we do not have observations at all the sites. The counts are assumed to be independent Poisson random variables whose means are given by a log Gaussian process. In this article, the Gaussian process is assumed to be either a Markov random field (MRF) or a geostatistical model, and we compare the two models on an environmental data set. To make the comparison, we calibrate priors for the parameters in the geostatistical model to priors for the parameters in the MRF. The calibration is obtained empirically. The main goal is to predict the hidden Poisson-mean process at all sites on the lattice, given the spatially irregular count data; to do this we use an efficient MCMC. The spatial Bayesian methods are illustrated on radioactivity counts analyzed by Diggle et al. (1998).

Hydrogen sulfide and particle matter levels associated with increased dispensing of anti-asthma drugs in Iceland's capital

BACKGROUND Air pollutants in Icelands capital area include hydrogen sulfide (H2S) emissions from geothermal power plants, particle pollution (PM10) and traffic-related pollutants. Respiratory health effects of exposure to PM and traffic pollutants are well documented, yet this is one of the first studies to investigate short-term health effects of ambient H2S exposure. OBJECTIVES The aim of this study was to investigate the associations between daily ambient levels of H2S, PM10, nitrogen dioxide (NO2) and ozone (O3), and the use of drugs for obstructive pulmonary diseases in adults in Icelands capital area. METHODS The study period was 8 March 2006 to 31 December 2009. We used log-linear Poisson generalized additive regression models with cubic splines to estimate relative risks of individually dispensed drugs by air pollution levels. A three-day moving average of the exposure variables gave the best fit to the data. Final models included significant covariates adjusting for climate and influenza epidemics, as well as time-dependent variables. RESULTS The three-day moving average of H2S and PM10 levels were positively associated with the number of individuals who were dispensed drugs at lag 3-5, corresponding to a 2.0% (95% confidence interval [CI] 0.4, 3.6) and 0.9% (95% CI 0.1, 1.8) per 10 μg/m3 pollutant concentration increase, respectively. CONCLUSION Our findings indicated that intermittent increases in levels of particle matter from traffic and natural sources and ambient H2S levels were weakly associated with increased dispensing of drugs for obstructive pulmonary disease in Icelands capital area. These weak associations could be confounded by unevaluated variables hence further studies are needed.

A Statistical Approach to Identify Ancient Template DNA

One of the key problems in the study of ancient DNA is that of authenticating sequences obtained from PCR amplifications of highly degraded samples. Contamination of ancient samples and postmortem damage to endogenous DNA templates are the major obstacles facing researchers in this task. In particular, the authentication of sequences obtained from ancient human remains is thought by many to be rather challenging. We propose a novel approach, based on the c statistic, that can be employed to help identify the sequence motif of an endogenous template, based on a sample of sequences that reflect the nucleotide composition of individual template molecules obtained from ancient tissues (such as cloned products from a PCR amplification). The c statistic exploits as information the most common form of postmortem damage observed among clone sequences in ancient DNA studies, namely, lesion-induced substitutions caused by cytosine deamination events. Analyses of simulated sets of templates with miscoding lesions and real sets of clone sequences from the literature indicate that the c-based approach is highly effective in identifying endogenous sequence motifs, even when they are not present among the sampled clones. The proposed approach is likely to be of general use to researchers working with DNA from ancient tissues, particularly from human remains, where authentication of results has been most challenging.

Decreased Incidence of Respiratory Infections in Children After Vaccination with Ten-valent Pneumococcal Vaccine.

Introduction: Respiratory tract infections (RTIs) and antibiotic usage are common in children, increasing the risk of antibacterial resistance. The introduction of protein-conjugated pneumococcal vaccines has led to reduction in pneumococcal infections. In 2011, pneumococcal protein-conjugated vaccine-10 was introduced into the national childhood vaccination in Iceland, a population not earlier vaccinated against pneumococcus, with 95% vaccine uptake in the first year. The aim of the study was to evaluate the number of children visiting the Children’s Hospital Iceland for RTIs before and after the introduction of the vaccine Methods: Admissions and visits to the Children’s Hospital because of RTIs were recorded, and children aged 3 months to 2 years in the nonvaccine eligible cohort (born 2008–2010) were compared with the vaccine eligible cohort (born in 2011). Statistical analysis was done using large sample Z test and incidence rate ratios (IRRs) were calculated. Results: A significant reduction in incidence rate was found when comparing the nonvaccine eligible cohort with the vaccine eligible cohort, both for acute otitis media (AOM) (IRR: 0.76; 95% confidence interval: 0.67–0.87; P < 0.0001) and for pneumonia (IRR: 0.77; 95% confidence interval: 0.64–0.95; P < 0.01). Conclusion: A significant reduction in hospital visits because of AOM and pneumonia in children vaccinated with pneumococcal protein-conjugated vaccine-10 was established. The abrupt and significant reduction of AOM is unusually clear. This reduction was noted very early after initiation of the vaccination.

Psychometric development of the Iceland-Family Perceived Support Questionnaire (ICE-FPSQ).

Valid and reliable instruments are needed to measure how family members perceive support from nurses when a family member is experiencing serious illness. The purpose of this article is to describe the development and psychometric testing of a new instrument, the Iceland-Family Perceived Support Questionnaire (ICE-FPSQ). The concepts in the original version of the ICE-FPSQ (suggesting 24 items and 4 categories) were developed from the Calgary Family Intervention Model. In the first phase of the instrument construction, 179 family members answered the original ICE-FPSQ, and 236 answered the questionnaire in the second phase of testing. Principal Component Analysis (PCA) reduced the original questionnaire to 21 items. Cronbach’s α = .959 explained 68% of the total variance, with three factors emerging: (a) emotional support (α = .925), (b) recognition of families’ strengths (α = .926), and (c) cognitive support (α = .841). Confirmatory Factor Analyses (CFA) resulted in a final version of the questionnaire containing 14 items with total alpha of .961 and two factors: (a) cognitive support (α = .881) and (b) emotional support (α = .952). The instrument measures family’s perceptions of support provided by nurses and will be helpful in examining the usefulness of family nursing interventions.

A long-term follow-up of allergic diseases in Iceland.

To cite this article: Finnbogadóttir AF, Árdal B, Eiríksson H, Hrafnkelsson B, Valdimarsson H, Lúðvíksson BRúnar, Haraldsson Á. A long‐term follow‐up of allergic diseases in Iceland. Pediatr Allergy Immunol 2012 Doi: 10.1111/j.1399‐3038.2011.01234.x

Psychometric Development of the Iceland-Expressive Family Functioning Questionnaire (ICE-EFFQ):

Instruments that are able to capture changes related to an intervention are of great value to the scientific as well as to the clinical community. The Iceland-Expressive Family Functioning Questionnaire (ICE-EFFQ) measures expressive emotions, collaboration, problem solving, communication, and behavior in families experiencing a chronic or an acute illness. The conceptual framework of the Calgary Family Assessment Model (Wright & Leahey, 2009) was used to construct the original questionnaire of 45 items and 10 subcategories. A total of 557 family members with a recent illness experience of a close relative answered the ICE-EFFQ in three different studies. Principal component factor analysis reduced the original questionnaire to 22 items with five factors emerging and a total Cronbach’s alpha coefficient of α = 0.912 accounting for 60.3% of the total variability. Confirmatory factor analysis from two studies produced the final version of the questionnaire consisting of 17 items and four factors.