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Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.
We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences.
We found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment.
Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.
Iodine is an essential micronutrient and an integral part of the thyroid hormones. In women of childbearing age, the estimated average iodine requirement is 95 μg/day and the recommended daily intake is 150 μg/day. While severe iodine deficiency poses reproductive risks, including infertility and abortions, the potential impact of mild-to-moderate iodine deficiency on subfecundity is unknown.
We examined whether iodine intake was associated with risk of subfecundity (i.e. > 12 months trying to get pregnant) in a large cohort of mild-to-moderately iodine deficient women.
Women enrolled in the Norwegian Mother and Child Cohort Study in gestational week 15 were asked to report whether the pregnancy was planned and how many months the couple had sexual relations without any contraception before getting pregnant. Information about time to pregnancy, maternal characteristics and iodine intake was available for 56,416 planned pregnancies. The median (interquartile range) time to pregnancy was 1.5 (0.5–6.0) months and the prevalence of subfecundity was 10.8%). We used iodine intake assessed by a validated food frequency questionnaire administered in pregnancy as a proxy for long-term (pre-pregnancy) iodine intake. We used logistic regression to estimate the association between iodine intake and subfecundity, using flexible modelling with restricted cubic splines, and adjusted for maternal age, BMI, parity, education, smoking status, energy intake and fiber intake. The median calculated iodine intake was 121 μg/day and the median urinary iodine concentration in a subsample of n = 2795 women was 69 μg/L.
The prevalence of subfecundity was lowest for iodine intakes ~100 μg/day and increased at lower intakes (p overall = 0.005). Compared to an intake of 100 μg/day (reference), intakes ~75 μg/day was associated with 5% (95%CI: 1%, 9%) higher prevalence and intakes ~50 μg/day with 14% (95%CI: 4%, 26%) higher prevalence. Use of dietary supplements was recorded only for the last 6 months prior to conception and women were included in the analysis regardless of their reported supplement use. In a sensitivity analysis, we excluding women who reported iodine-containing supplement use in the period 26–9 weeks before conception and the result remained unchanged. We also modelled time to pregnancy by Cox regression, and the result was consistent with the result for subfecundity.
The only good dietary sources of iodine in Norway are milk and white fish, and many women of fertile age have low intakes of these food items. This study shows that low habitual iodine intake may be a risk factor for subfecundity.
Iodine is essential in foetal development through being an integral part of the thyroid hormones. Severe iodine deficiency is associated with foetal growth restriction and preterm delivery. Less is known about the potential impact of mild-to-moderate iodine deficiency on these outcomes.
The aim of this study was to investigate whether maternal iodine intake in pregnancy was associated with birth weight (BW) z-score (i.e. BW adjusted for gestational length and sex) and preterm delivery (before week 37).
The study population included 77,995 singleton pregnancies from The Norwegian Mother and Child Cohort Study recruited in gestational week 15 in the period 2002–2008. Habitual iodine intake was calculated from a validated food frequency questionnaire covering the first half of pregnancy. Use of supplements was reported in questionnaires. Urinary iodine concentration (UIC) was measured in gestational week 18 in a subsample of n = 2795 women. Median iodine intake from food was 121 μg/day and median UIC was 69 μg/L. Median UIC < 150 μg/L is considered insufficient in pregnant women. Median birthweight was 3610 g and 5.0% were born before gestational week 37. Associations were modelled flexibly by use of restricted cubic splines, and adjusted for age, parity, pre-pregnancy BMI, education, smoking in pregnancy, energy intake, and fibre intake.
In non-users of iodine-containing supplements (n = 48,958), a low habitual iodine intake from food (lower than about 150 μg/day) was associated with a lower mean BW z-score (p < 0.001). Compared to an intake of 150 μg/day (reference), mean z-score was 0.04 SD lower at 100 μg/day and 0.12 SD lower at 75 μg/day. Results were similar when using UIC as the exposure (n = 2795, p = 0.017). Any use of iodine containing supplements in pregnancy was associated with 0.03 (95% CI: 0.01, 0.04) SD increase in BW z-score compared to no use (n = 77,949, p < 0.001).
A low habitual iodine intake from food (lower than about 100 μg/day) was associated with increased risk of preterm delivery (p = 0.003). Compared to an intake of 100 μg/day (reference), 75 μg/day was associated with 10% increased risk, and 50 μg/day with 28% increased risk. Use of an iodine-containing supplement was not associated with the risk of preterm delivery (OR: 0.97 (95%CI: 0.91, 1.04, p = 0.42)).
Inadequate iodine intake is prevalent in women of childbearing age in otherwise well-nourished populations. Our results indicate that mild-to-moderate iodine deficiency in pregnancy is associated with restricted foetal growth and increased risk of preterm delivery.
Work incapacity is a major public health challenge and an economic burden to both society and individuals. Understanding the underlying causes is becoming ever more relevant as many countries face an aging workforce. We examined stability and change in genetic and environmental factors influencing work incapacity from age 18 until retirement, and sex differences in these effects. The large population-based sample comprised information from 28,759 twins followed for up to 23 years combined with high-quality national registry data. We measured work incapacity as the total proportion of potential workdays lost due to sickness absence, rehabilitation and disability benefits. Structural equation modeling with twin data indicated moderate genetic influences on work incapacity throughout life in both men and women, with a high degree of genetic stability from young to old adulthood. Environmental influences were mainly age-specific. Our results indicate that largely the same genetic factors influence individual differences in work incapacity throughout young, middle and older adulthood, despite major differences in degree of work incapacity and probable underlying medical causes.
Early identification and diagnosis is beneficial for children with autism spectrum disorder (ASD). Universal early screening is recommended by many experts, but disputed because evidence is limited, and sensitivity and specificity in general populations are largely unknown.
To estimate the sensitivity and specificity of early population-based screening for ASDs.
The study was based on the Norwegian Mother and Child Cohort Study. The 36-month cohort questionnaire included the Social Communication Questionnaire (SCQ), a 40-item screening instrument for ASD.
A total of 58 520 mothers (58%) responded to the questionnaire. By the end of follow-up on 31 December 2015, 385 (0.7%) individuals with ASD had been identified among the responders' children. The distributions of SCQ scores in those with ASD and other children had large degrees of overlap. With the cut-off of 15 recommended in the SCQ manual, screening sensitivity was 20% (95% CI 16–24) for ASD overall. For children with ASD who had not developed phrase speech at 36 months, sensitivity was 46% (95% CI 35–57%), whereas it was 13% (95% CI 9–17) for children with ASD with phrase speech. Screening specificity was 99% (95% CI 99–99). With the currently recommended cut-off of 11, sensitivity increased to 42% for ASD overall (95% CI 37–47), 69% (95% CI 58–79) for ASD without phrase speech and 34% (95% CI 29–40) for ASD with phrase speech. Specificity was then reduced to 89% (95% CI 89–90).
Early ASD screening with a parent checklist had low sensitivity. It identified mainly individuals with ASD with significant developmental delay and captured very few children with ASD with cognitive skills in the normal range. Increasing sensitivity was not possible without severely compromising specificity.
Declaration of interest
C.L. receives royalty for the Social Communication Questionnaire, which she has co-authored.
The new species Austrella isidioidea, which is unique in the genus in having isidioid structures on the thallus lobe ends as well as apothecia lacking a thalline margin, is described from the Falkland Islands. A collection with an identical mtSSU rDNA sequence to A. arachnoidea but with significant morphological differences (viz. a variable apothecial margin ranging from an arachnoid hyphal weft to a corticated regular margin) is reported from Îles Kerguelen. The phylogenetic and biogeographical implications of these new records are discussed.
The present study investigates the photobiont diversity of the boreal felt lichen, Erioderma pedicellatum. Previously sampled genetic data from Newfoundland were reanalyzed and new sequence data (16S rDNA, rbcLX) of the boreal felt lichen from Alaska (USA), Kamchatka (Russia), and North Trøndelag (Norway) were generated. The highest genetic diversity of the photobiont is found in Alaska and Kamchatka, indicating that these may be the primary sources of the species in the Northern Hemisphere. In Newfoundland, the photobiont of E. pedicellatum was screened on leaves of the symbiotic liverwort Frullania asagrayana and it was found to occur on trees where no other lichens were present, demonstrating that the geographical distribution, and possibly also the ecological requirement of the photobiont of E. pedicellatum, is wider than that of the lichen phenotype. Finally, a postulated association between the occurrence of the vegetatively reproducing Coccocarpia palmicola and the occurrence of the compatible photobiont of E. pedicellatum on the same tree could not be established.
It is well-established that dynamics are central to protein function; their importance is implicitly acknowledged in the principles of the Monod, Wyman and Changeux model of binding cooperativity, which was originally proposed in 1965. Nowadays the concept of protein dynamics is formulated in terms of the energy landscape theory, which can be used to understand protein folding and conformational changes in proteins. Because protein dynamics are so important, a key to understanding protein function at the molecular level is to design experiments that allow their quantitative analysis. Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited for this purpose because major advances in theory, hardware, and experimental methods have made it possible to characterize protein dynamics at an unprecedented level of detail. Unique features of NMR include the ability to quantify dynamics (i) under equilibrium conditions without external perturbations, (ii) using many probes simultaneously, and (iii) over large time intervals. Here we review NMR techniques for quantifying protein dynamics on fast (ps-ns), slow (μs-ms), and very slow (s-min) time scales. These techniques are discussed with reference to some major discoveries in protein science that have been made possible by NMR spectroscopy.
Reports of ‘Psoroma sphinctrinum’ from Palaeotropical areas are shown to represent instead species of the genus Gibbosporina, which is described here as new to science. This genus is superficially similar to tripartite, austral Pannaria species, such as the species now referred to as Pannaria sphinctrina (Mont.) Tuck. ex Hue. A phylogram based on an analysis of the nuclear large subunit rDNA (LSU) locus shows that Gibbosporina is instead a clade in a Pannariaceae branch referred to as the ‘Physma group’, a most unexpected addition to Pannariaceae dealt with by several previous studies. Genera assigned to this group have very contrasting general appearances. However, this diverse group shares distinctly ring-like thalline excipular margins; strongly amyloid internal ascus structures; well-developed perispores which have irregular gibbae and/or nodulose or acuminate apical extensions, but not verrucae; lacks TLC-detectable secondary compounds and have tropical distributions. Gibbosporina is the only tripartite genus in the group, with distinct, nodulose, placodioid, mini-fruticose to mini-foliose cephalodia with a high diversity of Nostoc cyanobionts. The cyanomorphs can apparently exist independently in some cases, although the apothecia on such cephalodia on a specimen from Réunion were unexpectedly found to belong to the chloromorph. The genus and related genera forming the ‘Physma group’ are probably evolutionarily old, and their weak affinity to the remaining part of Pannariaceae, concentrated in the Southern Hemisphere, is discussed. The genus includes 13 known species, and the generitype is Gibbosporina boninensis from the Japanese Ogasawara Islands, originally described as Psoroma boninense and recombined here. The following 12 species are described here as new to science, seven of them with molecular support in an LSU and ITS-based phylogram: Gibbosporina acuminata (Australia, the Philippines), G. amphorella (New Caledonia), G. bifrons (Malaysia, New Caledonia, the Philippines, Solomon Islands), G. didyma (Mauritius, Réunion), G. elixii (Australia), G. leptospora (Australia, Papua New Guinea), G. nitida (Australia, Papua New Guinea, the Philippines), G. mascarena (Mauritius, Réunion, Sri Lanka), G. papillospora (the Philippines), G. phyllidiata (Solomon Islands), G. sphaerospora (Australia, Indonesia, Malaysia, the Philippines, Samoa, and with Psoroma sphinctrinum var. endoxanthellum as a new synonym), and G. thamnophora (Australia and the Philippines). Except for the phyllidiate G. phyllidiata and for G. thamnophora which has cephalodia adapted for vegetative propagation, the species are all primarily fertile. A key for determining the species is provided.
Flame spray pyrolysis (FSP) was applied to produce nanopowders of Ti1-xMxO2 and Sn1-xMxO2, where x = 0.05 and M = Nb/Sb, for use as catalyst support materials in PEM fuel cells/ electrolysers. FSP powders in the SnO2-IrO2 system were produced for the same applications. Homogenous particle size distribution (5-20 nm) was demonstrated by TEM, supported by BET and XRD analysis. Whereas two polymorphs were indicated for the Ti-based oxides, the Sb/Nb-doped SnO2 powders were single phase. FSP powders of Mn3O4 intended for supercapacitors were produced and the influence of the precursor/solvent mixtures on the physical and electrochemical properties evaluated.
Two novel memory polynomial models are derived based on physical knowledge of a general power amplifier (PA). The derivations are given in detail to facilitate derivations of other model structures. The model error in terms of normalized mean square error (NMSE) and adjacent channel error power ratio (ACEPR) of the novel model structures are compared to that of established models based on the number of parameters using data measured on two different amplifiers, one high-power base-station PA and one low-power general purpose amplifier. The novel models show both lower NMSE and ACEPR for any chosen number of parameters compared to the established models. The low model errors make the novel models suitable candidates for both modeling and digital predistortion.
To examine the association between calculated maternal dietary exposure to Hg in pregnancy and infant birth weight in the Norwegian Mother and Child Cohort Study (MoBa).
Exposure was calculated with use of a constructed database of Hg in food items and reported dietary intake during pregnancy. Multivariable regression models were used to explore the association between maternal Hg exposure and infant birth weight, and to model associations with small-for-gestational-age offspring.
The study is based on data from MoBa.
The study sample consisted of 62 941 women who answered a validated FFQ which covered the habitual diet during the first five months of pregnancy.
Median exposure to Hg was 0·15 μg/kg body weight per week and the contribution from seafood intake was 88 % of total Hg exposure. Women in the highest quintile compared with the lowest quintile of Hg exposure delivered offspring with 34 g lower birth weight (95 % CI −46 g, −22 g) and had an increased risk of giving birth to small-for-gestational-age offspring, adjusted OR = 1·19 (95 % CI 1·08, 1·30). Although seafood intake was positively associated with increased birth weight, stratified analyses showed negative associations between Hg exposure and birth weight within strata of seafood intake.
Although seafood intake in pregnancy is positively associated with birth weight, Hg exposure is negatively associated with birth weight. Seafood consumption during pregnancy should not be avoided, but clarification is needed to identify at what level of Hg exposure this risk might exceed the benefits of seafood.
We describe the importance of the Norwegian Twin Registry (NTR) for research in public health and provide examples from several programs of twin research at the Norwegian Institute of Public Health (NIPH), including the Nordic Twin Study of Cancer, our epigenetics platform, and our large program of research in mental health. The NTR has become an integral component of a national strategy for maximizing the research potential from Norwegian registries and biobank-based studies. The information provided herein builds upon and complements our recent report describing the establishment of the NTR and the cohorts comprising it. Although Norway has a long tradition in twin research, the centralization and administration of the twin data through a single register structure is fairly recent. The NTR was established in 2009 and currently includes 47,989 twins covering birth years 1895–1960 and 1967–1979; 31,440 of these twins have consented to participate in medical research (comprising 5,439 monozygotic pairs, 6,702 dizygotic same-sexed pairs, and 1,655 dizygotic opposite-sexed pairs). DNA from approximately 4,800 twins is banked at the NIPH biobank and new studies continuously add new data to the registry. The value of NTR data is greatly enhanced through record linkage possibilities offered by Norway's many nation-wide registries (medical, demographic, and socio-economic) and several studies are already taking advantage of these linkage opportunities for research.
Norway has a long-standing tradition in twin research, but the data collected in several population-based twin studies were not coordinated centrally or easily accessible to the scientific community. In 2009, the Norwegian Twin Registry was established at the Norwegian Institute of Public Health (NIPH) in Oslo with the purpose of creating a single research resource for Norwegian twin data. As of today, the Norwegian Twin Registry contains 47,989 twins covering birth years 1895–1960 and 1967–1979; 31,440 of these twins consented to participate in health-related research. In addition, DNA from approximately 4,800 of the twins is banked at the NIPH biobank and new studies are continually adding new data to the registry. The value of the Norwegian twin data is greatly enhanced by the linkage opportunities offered by Norway's many nationwide registries, spanning a broad array of medical, demographic, and socioeconomic information.