Lucía Colodro-Conde

Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci

Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form’s Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10−15) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

The Murcia Twin Registry: A Population-Based Registry of Adult Multiples in Spain

The Murcia Twin Registry (MTR) was created in 2006, under the auspices of the University of Murcia and the regional Health Authority, aiming to develop a research resource in Spain intended to stimulate current research and new investigation on the analysis of genetic factors related to health and health-related behaviors. The MTR development strategy was designed as a step-by-step process. Initially, it was focused on womens health but nowadays it includes males and opposite-sex twins. The database comprises 2,281 participants born between 1940 and 1966 in the region of Murcia, in Spain. There have been three waves of data collection and today the MTR databases include questionnaire and anthropometric data as well as biological samples. The current main areas of research interest are health and health-related behaviors, including lifestyle, health promotion, and quality of life. Future short-term development points to the completion of the biobank and continuing the collection of longitudinal data.

Relationship Between Level of Education and Breastfeeding Duration Depends on Social Context: Breastfeeding Trends Over a 40-Year Period in Spain

This article presents trends of breastfeeding in Spain from the 1960s to the end of the century, analyzing the relationship between level of education and breastfeeding duration. A sample of 666 adult women provided data about breastfeeding practices for children born between 1958 and 2002. Joinpoint regression models for breastfeeding duration for the firstborn child throughout these years show a U-shaped curve, with a sharp decrease at the beginning of the 1970s (−17.2%) and a gradual increase toward the end of the century (1.9%). However, the trend for women with primary studies shows a constant decrease throughout the whole period (−7.4%), while higher education levels relate to a positive trend from the 1970s onward (3.4%). The authors conclude that in the Spanish context, maternal level of education is not associated with breastfeeding duration in the same direction or with the same magnitude across time. Factors related to breastfeeding should be studied, taking into account social context.

Genetics and the environment affect the relationship between depression and low back pain: a co-twin control study of Spanish twins.

Abstract Although the co-occurrence of low back pain (LBP) and depression is common, the nature of this association remains unclear. We aimed to investigate whether symptoms of depression are associated with LBP after adjusting for various confounders, including genetics. We used cross-sectional data from 2148 twins from the Murcia Twin Registry, Spain. All twins answered questions about lifetime prevalence of LBP (outcome variable) and symptoms of depression, collected through two instruments, deriving 3 measures: (1) self-report feelings of depression and anxiety; (2) state depression, and (3) trait depression. First, associations were investigated using logistic regression analysis of the total sample. We performed subsequent matched within-pair twin case–control analyses with all complete twin pairs discordant for LBP regardless of zygosity, and separately for dizygotic and monozygotic pairs. This sequential analysis allows for more precise estimates of the relationship between variables, as in each step, the impact of early shared environment and genetics is further considered. Symptoms of depression and anxiety were associated with higher prevalence of LBP in the total sample analysis (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.31-2.05), and this relationship was stronger in the subsequent case–control analysis (OR, 1.74; 95% CI, 1.13-2.69) and dizygotic case–control analysis (OR, 2.39; 95% CI, 1.39-4.08) but disappeared when the analysis was conducted for monozygotic twins (OR, 0.92; 95% CI, 0.42-2.05). A similar pattern was found for state and trait depression. The depression–LBP relationship disappears when high levels of control for confounding factors are applied and seems to be driven by genetic or environmental factors that influence both conditions.

Heritability of initiation and duration of breastfeeding behavior

Breastfeeding is considered the best and most natural way of feeding infants during the first months of life. Breastfeeding has multiple short- and long-term benefits for the health of the mother and babies, and from an evolutionist standpoint, it would be a behavior worth preserving throughout time. The aim of the present study was to explore the relative influence of genetic and environmental factors in this behavior. Three hundred and ninety pairs of adult female twins provided information about whether they breastfed their children and for how long. Three variables were analyzed: initiation and duration for the first baby, and mean duration for the complete offspring. Polychoric correlations were consistently higher for monozygotic twins, supporting a role for genetic factors (0.50 [corrected] vs. 0.22 for initiation; 0.44 vs. 0.22 for duration in the first newborn; and 0.52 vs. 0.31 for duration on average). Model-fitting analyses found that in the best-fitting model, variance was explained by additive genetic and non-shared environmental factors, with estimated heritabilities ranging from 0.44 to 0.54 [corrected] in the measures studied. The rest of the variance would be due to unique environmental factors. We conclude that genetic factors have a significant impact on the complex behavior of breastfeeding.

Equality in Educational Policy and the Heritability of Educational Attainment.

Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents’ education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin.

Erratum: Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci

Correction to: Molecular Psychiatry 21, 749–757; doi:10.1038/mp.2016.49 The GWAS of neuroticism conducted within the Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute cohort did not include covariates of age, sex, genotyping batch and 10 principal components. Adding these covariates does not substantially change the pattern of results within the meta-analysis, but P-values for the nine reported loci have changed slightly (please see revised Figure 2, Table 2A and Table 2B).

Cohort Profile: Nausea and vomiting during pregnancy genetics consortium (NVP Genetics Consortium)

Nausea and vomiting during pregnancy (NVP), commonly known as morning sickness, is very common and is typically self-limiting. However, more severe forms and the development of hyperemesis gravidarum (HG), defined as persistent and excessive vomiting, with dehydration, ketonuria and >5% bodyweight loss,1 may lead to health consequences for the mother and the offspring exposed in utero. Despite efforts towards understanding the causes of NVP and HG, they are not well established. The NVP Genetics Consortium is an open collaborative network of researchers integrating data on NVP of women who have been pregnant at least once, with the goal of investigating NVP, NVP severity and HG. Currently, the NVP Genetics Consortium brings together data from Australia, Finland, Spain, the UK and Denmark. The Consortium is actively recruiting new members...

The GHQ-12 for the Assessment of Psychological Distress of Family Caregivers

This study examined the utility of the 12-item General Health Questionnaire (GHQ-12) to assess the psychological distress of family caregivers. To accomplish this goal, a sample of 172 caregivers, 25 men and 147 women, aged 56.6 (SD = 13.7) completed self-report questionnaires and provided data on demographic factors. Univariate and bivariate models adjust adequately, although the two-factor model (anxiety/depression and social dysfunction) presented a better fit. Relative caregivers scored higher in psychological distress (anxiety and depression levels) on the GHQ-12 than did the normal population. In conclusion, the GHQ-12 is a sensitive instrument to detect the presence of anxiety and depression in relative caregivers, and the external validity of the instrument is generally adequate. The GHQ-12 seems particularly appropriate for research and clinical and health intervention in caregivers. Implications and limitations of these results are discussed, along with suggestions for future research.

El Registro de Gemelos de Murcia. Un recurso para la investigación sobre conductas relacionadas con la salud

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia.