Heritability of head motion during resting state functional MRI in 462 healthy twins

Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% fema≤ 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD=3.16), range 16-29). Heritability estimates for three HM components-mean translation (MT), maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two-thirds (genetic correlations range 0.76-1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h2=42%). Using a sub-sample (N=35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent "traits" over repeated scans (r=0.53-0.59); reliability was even higher for the composite metric (r=0.66). In addition, phenotypic and cross-trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: h2-=0.23 (sd=0.041), BA45: h2-=0.26 (sd=0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated.

Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene

Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.

Genetic influences on brain asymmetry: A DTI study of 374 twins and siblings

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes. Here we analyzed 4. Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4 years ± 1.9 SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L > R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R > L) and about 10% for the forceps minor (L > R). Sex differences in asymmetry (men > women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry.

The multivariate A/C/E model and the genetics of fiber architecture

We present a new algorithm to compute the voxel-wise genetic contribution to brain fiber microstructure using diffusion tensor imaging (DTI) in a dataset of 25 monozygotic (MZ) twins and 25 dizygotic (DZ) twin pairs (100 subjects total). First, the structural and DT scans were linearly co-registered. Structural MR scans were nonlinearly mapped via a 3D fluid transformation to a geometrically centered mean template, and the deformation fields were applied to the DTI volumes. After tensor re-orientation to realign them to the anatomy, we computed several scalar and multivariate DT-derived measures including the geodesic anisotropy (GA), the tensor eigenvalues and the full diffusion tensors. A covariance-weighted distance was measured between twins in the Log-Euclidean framework [2], and used as input to a maximum-likelihood based algorithm to compute the contributions from genetics (A), common environmental factors (C) and unique environmental ones (E) to fiber architecture. Quanititative genetic studies can take advantage of the full information in the diffusion tensor, using covariance weighted distances and statistics on the tensor manifold.

Genetic architecture of subcortical brain regions: Common and region-specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1038; mean age=21.6±3.2years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region. This multivariate twin study identifies a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In parallel, it also describes substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52).

Cognitive functioning in older twins: The Older Australian Twins Study

Aim: To examine the concordance rates of common medical conditions and neurocognitive performance in monozygotic (MZ) and dizygotic (DZ) older twins. Methods: Twins aged ≥65 years and living in the three Eastern states of Australia were recruited through the Australian Twin Registry and underwent detailed neuropsychological and medical assessment. Results: Assessments were conducted on 113 MZ and 96 DZ twin pairs, with a mean age of 70.5 years. MZ twins were more concordant than DZ twins for hypertension and asthma. MZ twins had higher correlations than DZ twins on most neuropsychological tests, with the exception of some tests related to processing speed. The concordance rate for mild cognitive impairment or dementia was 76.2% in MZ twins and 42.9% in DZ twins, a non-significant difference. Conclusions: Except for some aspects of processing speed, most cognitive functions in older individuals show significant heritability. The heritability of neurocognitive disorders is, however, low.

Investigating brain connectivity heritability in a twin study using diffusion imaging data

Heritability of brain anatomical connectivity has been studied with diffusion-weighted imaging (DWI) mainly by modeling each voxel's diffusion pattern as a tensor (e.g., to compute fractional anisotropy), but this method cannot accurately represent the many crossing connections present in the brain. We hypothesized that different brain networks (i.e., their component fibers) might have different heritability and we investigated brain connectivity using High Angular Resolution Diffusion Imaging (HARDI) in a cohort of twins comprising 328 subjects that included 70 pairs of monozygotic and 91 pairs of dizygotic twins. Water diffusion was modeled in each voxel with a Fiber Orientation Distribution (FOD) function to study heritability for multiple fiber orientations in each voxel. Precision was estimated in a test-retest experiment on a sub-cohort of 39 subjects. This was taken into account when computing heritability of FOD peaks using an ACE model on the monozygotic and dizygotic twins. Our results confirmed the overall heritability of the major white matter tracts but also identified differences in heritability between connectivity networks. Inter-hemispheric connections tended to be more heritable than intra-hemispheric and cortico-spinal connections. The highly heritable tracts were found to connect particular cortical regions, such as medial frontal cortices, postcentral, paracentral gyri, and the right hippocampus.

Susceptibility to ankylosing spondylitis in twins: The role of genes, HLA, and the environment

Objective To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). Methods Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence- specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. Results Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co- twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. Conclusion Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

Genetic control of bone density and turnover: Role of the collagen 1α1, estrogen receptor, and vitamin D receptor genes

Genetic factors are known to influence both the peak bone mass and probably the rate of change in bone density. A range of regulatory and structural genes has been proposed to be involved including collagen 1α1 (COL1A1), the estrogen receptor (ER), and the vitamin D receptor (VDR), but the actual genes involved are uncertain. We therefore studied the role of the COL1A1 and VDR loci in control of bone density by linkage in 45 dizygotic twin pairs and 29 nuclear families comprising 120 individuals. The influences on bone density of polymorphisms of COL1A1, VDR, and ER were studied by association both cross-sectionally and longitudinally in 193 elderly postmenopausal women (average age, 69 years) over a mean follow-up time of 6.3 years. Weak linkage of the COL1A1 locus with bone density was observed in both twins and families (p = 0.02 in both data sets), confirming previous observations of linkage of this locus with bone density. Association between the MscI polymorphism of COL1A1 and rate of lumbar spine bone loss was observed with significant gene-environment interaction related to dietary calcium intake (p = 0.0006). In the lowest tertile of dietary calcium intake, carriers of "s" alleles lost more bone than "SS" homozygotes (p = 0.01), whereas the opposite was observed in the highest dietary calcium intake (p = 0.003). Association also was observed between rate of bone loss at both the femoral neck and the lumbar spine and the TaqI VDR polymorphism (p = 0.03). This association was strongest in those in the lowest tertile of calcium intake, also suggesting the presence of gene-environment interaction involving dietary calcium and VDR, influencing bone turnover. No significant association was observed between the PvuII ER polymorphism alone or in combination with VDR or COL1A1 genotypes, with either bone density or its rate of change. These data support the involvement of COL1A1 in determination of bone density and the interaction of both COL1A1 and VDR with calcium intake in regulation of change of bone density over time.

Identtisten ja epäidenttisten kaksosten puhe : Monotsygoottisten ja ditsygoottisten kaksosten puheen vertailua kesto-, nopeus-, tauko- ja taajuusmittauksin

This thesis presents an experimental study of the speech prosody of identical and non-identical twins. Speech fluency, pauses, speech rate, utterance length and speech frequency were examined phonetically, auditorily, semantically and statistically. The methods included both reading tasks (reading the alphabet, numerical lists, sentences with foreign loan words, holiday theme questions as well as 1.5 pages of text with long sentences and complex words) and spontaneous speech tasks (picture description and answering holiday theme questions). The subjects were Finnish-speaking 22-28-year-old female twins: 8 identical (monozygotic) and 10 non-identical (dizygotic) pairs. One pair was male-female. Comparisons were made between twin groups and between sisters. The data was regathered from four twin pairs, to make it possible to investigate some subjects intra-individually. In addition phoneticians, phonetic students and people without knowledge of phonetic science were tested in two listening experiments. The results showed that the dizygotic twins differed more from each other than monozygotic twins and that monozygotic twin sisters shared more similarities than dizygotic twin sisters. For example, between monozygotic twin sisters smaller differences were found between word count, utterance length and speech rate in spontaneous speech tasks. Dizygotic twin sisters made more different kinds of reading mistakes with the same target words than monozygotic twin sisters, while monozygotic twin sisters made more of the same reading mistakes with the same target words than dizygotic twin sisters. The listening experiments showed that only professional phoneticians were able to recognize the twin sisters. Even though the twins had the possibility to freely choose their speech rate, pausing and speech frequency, they used their own speech patterns; these included the same average speech frequency, average speech rate, type of pausing routine or filled pauses, and other speech mannerisms throughout their speech.

Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Familial aggregation of type 1 diabetes and diabetic nephropathy in Finland

Type 1 diabetes (T1D) is a common, multifactorial disease with strong familial clustering. In Finland, the incidence of T1D among children aged 14 years or under is the highest in the world. The increase in incidence has been approximately 2.4% per year. Although most new T1D cases are sporadic the first-degree relatives are at an increased risk of developing the same disease. This study was designed to examine the familial aggregation of T1D and one of its serious complications, diabetic nephropathy (DN). More specifically the study aimed (1) to determine the concordance rates of T1D in monozygotic (MZ) and dizygotic (DZ) twins and to estimate the relative contributions of genetic and environmental factors to the variability in liability to T1D as well as to study the age at onset of diabetes in twins; (2) to obtain long-term empirical estimates of the risk of T1D among siblings of T1D patients and the factors related to this risk, especially the effect of age at onset of diabetes in the proband and the birth cohort effect; (3) to establish if DN is aggregating in a Finnish population-based cohort of families with multiple cases of T1D, and to assess its magnitude and particularly to find out whether the risk of DN in siblings is varying according to the severity of DN in the proband and/or the age at onset of T1D: (4) to assess the recurrence risk of T1D in the offspring of a Finnish population-based cohort of patients with childhood onset T1D, and to investigate potential sex-related effects in the transmission of T1D from the diabetic parents to their offspring as well as to study whether there is a temporal trend in the incidence. The study population comprised of the Finnish Young Twin Cohort (22,650 twin pairs), a population-based cohort of patients with T1D diagnosed at the age of 17 years or earlier between 1965 and 1979 (n=5,144) and all their siblings (n=10,168) and offspring (n=5,291). A polygenic, multifactorial liability model was fitted to the twin data. Kaplan-Meier analyses were used to provide the cumulative incidence for the development of T1D and DN. Cox s proportional hazards models were fitted to the data. Poisson regression analysis was used to evaluate temporal trends in incidence. Standardized incidence ratios (SIRs) between the first-degree relatives of T1D patients and background population were determined. The twin study showed that the vast majority of affected MZ twin pairs remained discordant. Pairwise concordance for T1D was 27.3% in MZ and 3.8% in DZ twins. The probandwise concordance estimates were 42.9% and 7.4%, respectively. The model with additive genetic and individual environmental effects was the best-fitting liability model to T1D, with 88% of the phenotypic variance due to genetic factors. The second paper showed that the 50-year cumulative incidence of T1D in the siblings of diabetic probands was 6.9%. A young age at diagnosis in the probands considerably increased the risk. If the proband was diagnosed at the age of 0-4, 5-9, 10-14, 15 or more, the corresponding 40-year cumulative risks were 13.2%, 7.8%, 4.7% and 3.4%. The cumulative incidence increased with increasing birth year. However, SIR among children aged 14 years or under was approximately 12 throughout the follow-up. The third paper showed that diabetic siblings of the probands with nephropathy had a 2.3 times higher risk of DN compared with siblings of probands free of nephropathy. The presence of end stage renal disease (ESRD) in the proband increases the risk three-fold for diabetic siblings. Being diagnosed with diabetes during puberty (10-14) or a few years before (5-9) increased the susceptibility for DN in the siblings. The fourth paper revealed that of the offspring of male probands, 7.8% were affected by the age of 20 compared with 5.3% of the offspring of female probands. Offspring of fathers with T1D have 1.7 times greater risk to be affected with T1D than the offspring of mothers with T1D. The excess risk in the offspring of male fathers manifested itself through the higher risk the younger the father was when diagnosed with T1D. Young age at onset of diabetes in fathers increased the risk of T1D greatly in the offspring, but no such pattern was seen in the offspring of diabetic mothers. The SIR among offspring aged 14 years or under remained fairly constant throughout the follow-up, approximately 10. The present study has provided new knowledge on T1D recurrence risk in the first-degree relatives and the risk factors modifying the risk. Twin data demonstrated high genetic liability for T1D and increased heritability. The vast majority of affected MZ twin pairs, however, remain discordant for T1D. This study confirmed the drastic impact of the young age at onset of diabetes in the probands on the increased risk of T1D in the first-degree relatives. The only exception was the absence of this pattern in the offspring of T1D mothers. Both the sibling and the offspring recurrence risk studies revealed dynamic changes in the cumulative incidence of T1D in the first-degree relatives. SIRs among the first-degree relatives of T1D patients seems to remain fairly constant. The study demonstrates that the penetrance of the susceptibility genes for T1D may be low, although strongly influenced by the environmental factors. Presence of familial aggregation of DN was confirmed for the first time in a population-based study. Although the majority of the sibling pairs with T1D were discordant for DN, its presence in one sibling doubles and presence of ESRD triples the risk of DN in the other diabetic sibling. An encouraging observation was that although the proportion of children to be diagnosed with T1D at the age of 4 or under is increasing, they seem to have a decreased risk of DN or at least delayed onset.

Male eating disorders and related traits : Genetic epidemiological study in Finnish twins

The aim of this study was to deepen the understanding of eating disorders, body image dissatisfaction and related traits in males by examining the epidemiology and genetic epidemiology of these conditions in representative population-based twin samples. The sample of Study I included adolescent twins from FinnTwin12 cohorts born 1983 87 and assessed by a questionnaire at ages 14 y (N=2070 boys, N=2062 girls) and 17 y (N=1857 boys, N=1984 girls). Samples of Studies II-V consisted of young adult twins born 1974-79 from FinnTwin16 cohorts (Study II N=1245 men, Study III N=724 men, Study IV N=2122 men, Study V N=2426 women and N=1962 men), who were assessed by a questionnaire at the age 22-28 y. In addition, 49 men and 526 women were assessed by a diagnostic interview. The overall response rates for both twin cohorts in all studies were 80-90%. In boys, mainly genetic factors (82%, 95% confidence interval [CI] 72-92) explained the covariation of self-esteem between the ages 14 y and 17 y, whereas in girls, environmental factors (69%, 95% CI 43-93) were the largest contributors. Of young men, 30% experienced high muscle dissatisfaction, while 12% used or had used muscle building supplements and/or anabolic steroids on a regular basis. Muscle dissatisfaction exhibited a robust association with the indicators of mental distress and a genetic component (42%, 95% CI 23-59) for its liability in this population was found. The variation of muscle-building substance use was primarily explained by the environmental factors. The incidence rate of anorexia nervosa in males for the age of 10-24 y was 15.7 (95% CI 6.6-37.8) per 100 000 person-years, and its lifetime prevalence by the young adulthood was 0.24% (95% CI 0.03-0.44). All detected probands with anorexia nervosa had recovered from eating disorders, but suffered from substantial psychiatric comorbidity, which manifested also in their co-twins. Additionally, male co-twins of the probands displayed significant dissatisfaction with body musculature, a male-specific feature of body dysmorphic disorder. All probands were from twin pairs discordant for eating disorders. Of the five male probands with anorexia nervosa, only one was from an opposite-sex twin pair. Among women from the opposite-sex pairs, the prevalence of DSM-IV or broad anorexia nervosa was no significantly different compared to that of the women from monozygotic pairs or from dizygotic same-sex pairs. The prevalence of DSM-IV or broad bulimia nervosa did not differ in opposite- versus same-sex female twin individuals either. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite-sex and same-sex pairs. In adolescence, development of self-esteem was differently regulated in boys compared to girls: this finding may have far-reaching implications on the etiology of sex discrepancy of internalizing and externalizing disorders. In young men, muscle dissatisfaction and muscle building supplement/steroid use were relatively common. Muscle dissatisfaction was associated with marked psychological distress such as symptoms of depression and disordered eating. Both genetic and environmental factors explained muscle dissatisfaction in the population, but environmental factors appeared to best explain the use of muscle-building substances. In this study, anorexia nervosa in boys and young men from the general population was more common, transient and accompanied by more substantial co-morbidity than previously thought. Co-twins of the probands with anorexia nervosa displayed significant psychopathology such as male specific symptoms of body dysmorphic disorder, but none of them had had an eating disorder: taken together, these traits are suggestive for an endophenotype of anorexia nervosa in males. Little evidence was found on that the risk for anorexia nervosa, bulimia nervosa, disordered eating or body dissatisfaction were associated with twin zygosity. Thus, it is unlikely that in utero femininization, masculinization or postnatal socialization according to the sex of the co-twin have a major influence on the later development of eating disorders or related traits.

Noise sensitivity medical, psychological and genetic aspects

Noise can be defined as unwanted sound. It may adversely affect the health and well-being of individuals. Noise sensitivity is a personality trait covering attitudes towards noise in general and a predictor of noise annoyance. Noise sensitive individuals are more affected by noise than less sensitive individuals. The determinants and characteristics related to noise sensitivity are rather poorly known. The risk of health effects caused by noise can be hypothesized to be higher for noise sensitive individuals compared to those who are not noise sensitive. A cardiovascular disease may be an example of outcomes. The general aim of the present study was to investigate the association of noise sensitivity with specific somatic and psychological factors, including the genetic component of noise sensitivity, and the association of noise sensitivity with mortality. The study was based on the Finnish Twin Cohort of same-sex twin pairs born before 1958. In 1988 a questionnaire was sent to twin pairs discordant for hypertension. 1495 individuals (688 men, 807 women) aged 31 88 years replied, including 573 twin pairs. 218 of the subjects lived in the Helsinki Metropolitan Area. Self-reported noise sensitivity, lifetime noise exposure and hypertension were obtained from the questionnaire study in 1988 and other somatic and psychological factors from the questionnaire study in 1981 for the same individuals. In addition, noise map information (1988 1992) from the Helsinki Metropolitan Area and mortality follow-up 1989 2003 were used. To evaluate the stability and validity of noise sensitivity, a new questionnaire was sent in 2002 to a sample of the subjects who had replied to the 1988 questionnaire. Of all subjects who had answered the question on noise sensitivity, 38 % were noise sensitive. Noise sensitivity was independent of noise exposure levels indicated in noise maps. Subjects with high noise sensitivity reported more transportation noise exposure than subjects with low noise sensitivity. Noise sensitive subjects reported transportation noise exposure outside the environmental noise map areas almost twice as often as non-sensitive subjects. Noise sensitivity was associated with hypertension, emphysema, use of psychotropic drugs, smoking, stress and hostility, even when lifetime noise exposure was adjusted for. Monozygotic twin pairs were more similar with regards noise sensitivity than dizygotic twin pairs, and quantitative genetic modelling indicated significant familiality. The best fitting genetic model provided an estimate of heritability of 36 %. Follow-up of subjects in the case-control study showed that cardiovascular mortality was significantly increased among noise sensitive women, but not among men. For coronary heart mortality the interaction of noise sensitivity and lifetime noise exposure was statistically significant in women. In conclusion, noise sensitivity has both somatic and psychological components. It does aggregate in families and probably has a genetic component. Noise sensitivity may be a risk factor for cardiovascular mortality in women.

The shared genetics of migraine and anxious depression

OBJECTIVES To investigate: - (1) whether shared genetic factors influence migraine and anxious depression; - (2) whether the genetic architecture of migraine depends on anxious depression; - (3) whether the association between migraine and anxious depression is causal. BACKGROUND Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association. METHODS A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method. RESULTS Modest but significant phenotypic (rP=0.28), genetic (rG=0.30), and nonshared environmental (rE=0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship. CONCLUSIONS These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.