Familial Transmission Research Articles

Can Attention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood?

In this issue of JAMAPsychiatry, 2 large, longitudinal, population studies from Brazil1 and the United Kingdom2 propose aparadigmatic shift in ourunderstandingof attention-deficit/ hyperactivity disorder (ADHD). They conclude, not only that theonsetofADHDcanoccur inadulthood,but that childhoodonset and adult-onset ADHDmay be distinct syndromes. Prior to thesepublications, thediagnosisofADHDinadults hadevolvedin2directions.Ameta-analysis3oflongitudinalstudiesdocumentedanage-dependentdecline in theexpressionof ADHDsymptoms.Two-thirds ofyouthwithADHDcontinued tohaveimpairingsymptomsof ADHDinyoungadulthood,despite only 15%meeting full diagnostic criteria for the disorder. TheBrazilianandUKstudies found theexpected rateofpersistence to ages 18 to 19 years: 17.2% and 21.9%%, respectively. A longitudinal population study4 from New Zealand observed a 4.9%persistencerateofADHDtoage38years.Practitioners take heed: these lowratesof casesmeeting fulldiagnostic criteria ignorethemuchhigherpersistencerateof impairingADHDsymptoms,which are relevant in clinical practice.3 In each study, the prevalence of adult-onset ADHD (Brazil, 10.3%1; UnitedKingdom, 5.5%2; andNewZealand, 2.7%4) wasmuch larger than theprevalenceof childhood-onset adult ADHD (United Kingdom, 2.6%; Brazil, 1.5%; and New Zealand, 0.3%). These estimates should be viewedwith caution. Theadults in theBrazil andUKstudieswereaged18 to 19years. That is too small a slice of adulthood to draw firm conclusions.Moreover, theratesofchildhood-onsetadultADHDseem too low.1All rates are below3.1%,which is the lower endof the 95% CI from a 10-country population study of adults.5 Why do the prospective studies of youth and population studies of adults disagree? One answer is the potential for recall biases in the latter studies.6 Another reason for disagreement is noted in theBrazilian study1: the “false-positive paradox.” This maxim states that, even when false-positive rates are low,many, or evenmost, diagnoses in a population study canbe false. For example, if theprevalenceofADHD is 5%and the false-positive rate is 5%, thenhalf thediagnoses in apopulation studywill be false. The false-positive rate is sensitive to the method of diagnosis. The child diagnoses in the studies fromBrazil,1 theUnitedKingdom,2 andNewZealand4used reports from parents and/or teachers, but the adult diagnoses were based on self-report. Self-reports of ADHD in adults are less reliable than informant reports, which is why the heritability of adult ADHD is low using self-reports but high using informant reports. In fact, theUKstudy foundavery lowheritability for adult ADHD (35%), which could be a sign of substantialmeasurementerrorandfalse-positivediagnoses.Of further concern, another longitudinal study6 found that current symptomsofADHDwereunderreportedbyadultswhohadhad ADHD in childhood and overreported by adults who did not haveADHD inchildhood.Because these concerns suggest that the UK, Brazilian, and New Zealand studies may have underestimated the persistence of ADHD and overestimated the prevalenceofadult-onsetADHD, itwouldbeamistake forpractitioners to assume that most adults referred to them with ADHD symptoms will not have a history of ADHD in youth. Theseconcernsdonotargueagainst theexistenceofadultonset ADHD or the idea that it is a clinically relevant syndrome. In fact, as a group, the adult-onset cases showed significant functional impairment. Moreover, one of the studies ruled out the idea that adult-onset ADHD is amisdiagnosis of another disorder. Further support for the validity of adultonset ADHD comes froma study of referred adultswho retrospectively reported childhood symptoms.7 Based on clinical features and familial transmission, that study concluded that onsetofADHDin lateadolescenceandearlyadulthood isvalid.7 The new articles proffer provocative conclusions: from Brazil,1 thatchildandadultADHDare“distinctsyndromes,”from theUnitedKingdom,2 “that adult ADHD ismore complex than a straightforward continuationof the childhooddisorder,” and fromNewZealand,4thatadultADHDis“notaneurodevelopmentaldisorder.”Theseconclusionsseempremature. Ineachstudy, adult-onset ADHD was de novo only in the sense that fullthresholdADHDhadnotbeendiagnosedby the investigatorsat priorassessments.IntheNewZealandstudy,comparedwithcontrols, theadult-onsetADHDgrouphadmoreteacher-ratedsymptoms of ADHD, more conduct disorder in childhood and were more likely to have had a combined parent-teacher report of ADHDsymptomonset prior to age 12 years. Likewise, the individuals in theadult-onsetADHDgroup in theUKstudyhadsignificantlyelevatedratesofADHDsymptoms, conductdisorder, andoppositionaldefiantdisorder inchildhood. In theBrazilian study,1 only 38% of participants with adult-onset ADHD were “neurotypical”asdefinedbyADHDandconductdisordersymptoms. Likewise, in a study of referred cases, one-third of lateadolescentandadult-onsetcaseshadchildhoodhistoriesofoppositionaldefiantdisorder,conductdisorder,andschoolfailure.7 Thus,many of the “adult onsets” of ADHD appear to have had neurodevelopmental roots. Theseneurodevelopmental rootspoint toanotherparadigm changerwhich, althoughnot discussed by these investigators, can be deduced from their data: the existence of subthreshold Related articles Opinion

Familial Transmission of Hospital-Treated Varicose Veins in Adoptees: A Swedish Family Study

Varicose veins (VVs) cluster in families, but the familial risk of VVs has not been determined among adoptees. The aim was to estimate whether the familial transmission of VVs is related to disease in biological and/or adoptive parents. The Swedish Multi-Generation Register and the Swedish Patient Register were used to follow all Swedish-born adoptees (born 1932 through 2004) that could be linked to both their biological and their adoptive parents (n= 80,214; 50% females). The risk of VVs was estimated in adoptees with at least 1 biological parent with VVs, but no adoptive parent with VVs (n= 187) compared with adoptees without a biological or adoptive parent with VVs (n= 1,758). The risk of VVs was also determined in adoptees with at least 1 adoptive parent, but no biological parent with VVs (n= 87), and in adoptees with both biological and adoptive parents affected (n= 21). Adoptees from an affected biological parent, but no adoptive parent, were more likely to have VVs than adoptees from an unaffected biological or adoptive parent (standard incidence ratio [SIR]= 2.21; 95% CI, 1.91-2.55). The familial SIR for adoptees with both an affected biological parent and an adoptive parent was 4.58 (95% CI, 2.83-7.01). Adoptees with an affected adoptive parent but no biological parent were not at increased risk of VVs (SIR= 1.15; 95% CI, 0.92-1.42). These novel findings suggest that genetic factors make a strong contribution to the familial transmission of VVs from parents to offspring, although familial environmental factors might contribute.

A Single Transcriptome of a Green Toad (Bufo viridis) Yields Candidate Genes for Sex Determination and -Differentiation and Non-Anonymous Population Genetic Markers.

Large genome size, including immense repetitive and non-coding fractions, still present challenges for capacity, bioinformatics and thus affordability of whole genome sequencing in most amphibians. Here, we test the performance of a single transcriptome to understand whether it can provide a cost-efficient resource for species with large unknown genomes. Using RNA from six different tissues from a single Palearctic green toad (Bufo viridis) specimen and Hiseq2000, we obtained 22,5 Mio reads and publish >100,000 unigene sequences. To evaluate efficacy and quality, we first use this data to identify green toad specific candidate genes, known from other vertebrates for their role in sex determination and differentiation. Of a list of 37 genes, the transcriptome yielded 32 (87%), many of which providing the first such data for this non-model anuran species. However, for many of these genes, only fragments could be retrieved. In order to allow also applications to population genetics, we further used the transcriptome for the targeted development of 21 non-anonymous microsatellites and tested them in genetic families and backcrosses. Eleven markers were specifically developed to be located on the B. viridis sex chromosomes; for eight markers we can indeed demonstrate sex-specific transmission in genetic families. Depending on phylogenetic distance, several markers, which are sex-linked in green toads, show high cross-amplification success across the anuran phylogeny, involving nine systematic anuran families. Our data support the view that single transcriptome sequencing (based on multiple tissues) provides a reliable genomic resource and cost-efficient method for non-model amphibian species with large genome size and, despite limitations, should be considered as long as genome sequencing remains unaffordable for most species.

Hyperaldosteronism: How to Discriminate Among Different Disease Forms?

Primary aldosteronism (PA), characterized by the inappropriate and abnormal adrenal secretion of aldosterone, is the most common cause of secondary hypertension. PA has been shown to increase cardiovasular and cerebrovascular risks in comparison with essential hypertension. PA is a multi-faceted disease, which comprises unilateral forms, benefitting from surgical treatment, and bilateral forms, which are the best managed medically. PA is more frequently sporadic, but in some cases, it displays a familial transmission pattern. For these reasons, it is important to diagnose PA early on and correctly distinguish and manage its different forms. In this review, we analyze the different forms of PA, with attention on the diagnostic pathway and the genetics of the disease.

Bilateral Agenesis of Permanent Mandibular Central Incisors: Two Familial Case Reports

Agenesis of one or more teeth is the most common anomaly of tooth development. Several factors like infection, trauma, metabolic disorders, radiation, environmental, genetic factors and idiopathic are possible etiological factors of congenital agenesis. Hypodontia usually requires comprehensive and complex treatments, ranging from single restorations to surgery and multiple restorations, associated with lifelong maintenance. A 9 year-old female and a 9 year-old male patient have reported to the clinic and we have detected agenesis of bilateral mandibular incisors with an oligodontia and a hypodontia with familial transmission. Although in many cases mentions oligodontia, congenitally missing bilateral mandibular central teeth cases has not been documented adequately. The purpose of this article is to present two cases of agenesis of bilateral mandibular incisors with hypodontia and oligodontia. Pediatric dentists must be capable of diagnosing because early diagnosis and guidance with regard to treatment are necessary for the problems that may affect the behavioral pattern and social life of these persons. Keywords: Agenesis; Congenital missing; Hypodontia; Non-syndromic; Oligodontia

Temperament and major depression: How does difficult temperament affect frequency, severity, and duration of major depressive episodes among offspring of parents with or without depression?

IntroductionThe current study examined the relationships between parental depression, offspring depression, and offspring temperament among 203 offspring of parents with or without depression. The specific aim was to investigate how parental depression and offspring difficult temperament affect frequency, severity, and duration of offspring major depressive episodes (MDEs). MethodsAs part of an ongoing multigenerational study assessing familial transmission of depression, offspring were assessed over a 20-year study period. Offspring temperament was assessed at baseline using the Dimensions of Temperament Survey and diagnostic interviews were conducted at each of the four waves using best estimate procedures. ResultsDifficult temperament predicted greater frequency of lifetime MDEs. Parental depression moderated the relationship between offspring difficult temperament and severity of MDEs, such that difficult temperament was associated with increased severity ratings among high-risk, but not low-risk offspring. Dimensional analysis revealed that lower rhythmicity and adaptability were associated with greater number of lifetime MDEs, higher inattention/distractibility was associated with shorter duration of MDEs, and greater activity was associated with decreased severity of MDEs. DiscussionCertain limitations must be noted, namely the self-report nature of temperament data and the relatively small sample size drawn from a clinical and predominantly Caucasian and Christian sample. Notwithstanding these limitations, our results suggest that the clinical presentation of major depression may reflect temperamental profiles and should be considered in diagnostic and treatment settings.

Children's Emotion Regulation Difficulties Mediate the Association Between Maternal Borderline and Antisocial Symptoms and Youth Behavior Problems Over 1 Year.

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are among the most debilitating psychiatric conditions. Behaviors and traits associated with these disorders can have profound influences on those surrounding the affected individual. Accordingly, researchers have begun to examine effects of these symptoms on parent-child relationships. Theoretical and empirical work suggests that one mechanism linking maternal psychopathology to child symptoms is familial transmission of emotion dysregulation. The authors examined children's emotion regulation difficulties as a mediator between maternal BPD/ASPD symptoms and child behavior problems 1 year later. Analyses revealed that a composite of maternal BPD/ASPD symptoms had a direct effect on child internalizing, externalizing, and total symptoms. Associations between maternal BPD/ASPD symptoms and youth problems were partially mediated by child emotion regulation difficulties, even with maternal depression and other relevant covariates included in the models. Thus, maternal BPD/ASPD symptoms and child emotion regulation difficulties represent potential targets for prevention of psychopathology among youth.

Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors.

This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls.

Factors associated with pterygium based on history and clinical examination of patients in Pakistan

PurposeThe purpose of this study was to determine the factors associated with Pterygium, utilizing history and examination. MethodsIn this prospective case series study, a total of 1227 patients with Pterygium presenting at the Department of Ophthalmology, Chandka Medical College Hospital Larkana, Pakistan, from January 1997 to January 2015 were included. A standard proforma containing proposed risk factors was filled in for every patient. Clinical examination was performed on slit-lamp biomicroscope to confirm presence of pterygium. ResultsOut of the total 1227 patients, 656 (53.46%) were males, and 571 (46.54%) were females. Mean age ± standard deviation was 53.12 years ± 15.85 years, and the age range was 20–79 years. 1063 (86.63%) patients belonged to areas with hot and dry weather, 421 (34.31%) patients had a positive family history for Pterygium, 740 (60.31%) patients had history of previous exposure to toxic chemicals, and 364 (29.67%) patients had dry eye. ConclusionThis study points towards the simultaneous role of multiple risk factors including sun exposure, hot climate, toxic material exposure, familial transmission, and dry eye in association with pterygium.

Self-Rated Depression Severity Relative to Clinician-Rated Depression Severity: Trait Stability and Potential Role in Familial Transmission of Suicidal Behavior

Self-rated depression and hopelessness severity are predictors of suicide attempt in major depression. This study evaluated whether: (1) greater self-rated distress relative to severity of clinician-rated depression is a trait; (2) that trait is familial; and (3) that trait is linked to familial transmission of suicidal behavior. A total of 285 mood disorder probands and 457 offspring were assessed twice, at least 1 year apart. Family and subject intra-class correlations for self-report depression and hopelessness, controlling for clinician-rated depression severity, were computed. Mixed general linear models determined offspring-proband correlations. Within-individual intra-class correlation (ICC) for depression-hopelessness was 37.8% (bootstrap 95% CI: 31.0–46.3%). Parent-offspring ICC was 10.7% (bootstrap 95% CI: 3.5–17.8%). Suicide attempt concordant parent-offspring correlation for subjective depression was positive, but negative for attempter parent and nonattempter offspring (p = .0213 for slope interaction). Pessimism was greater in proband or offspring attempters than proband or offspring nonattempters (p < .05). Self-reported hopelessness is partly trait-dependent, and there is modest familial transmission of self-reported depression linked to suicidal behavior that may partly explain familial transmission of suicidal behavior.

Characteristics of HBV transmission in families with HBsAg-positive fathers and familial clustering of HBV infection

To investigate the characteristics of hepatitis B virus (HBV) transmission among family members in families with familial clustering of HBV infection and poor outcomes, as well as the prevalence and distribution characteristics of HBsAg in offspring with different parental HBsAg status. The general information of each member in families with poor outcomes were collected from 2007 to 2010, and serological test was performed to analyze the prevalence and distribution of HBsAg in family members. The chi-square test or Fisher's exact test was used to analyze and compare the sex of offspring and the prevalence of HBsAg in them in 266 nuclear families with different paternal and maternal HBsAg status. The positive rates of HBsAg in parents, siblings, children, and spouses of the probands were 20%, 88.2%, 76.8%, and 9.5%, respectively. The nuclear families with HBsAg-positive fathers and HBsAg-negative mothers had a significantly increased proportion of male offspring (male/female ratio = 2.02) compared with those with HBsAg-positive mothers and HBsAg-negative fathers (1.22) or those with HBsAg-negative fathers and mothers (0.96). In addition, in the nuclear families with HBsAg-positive fathers and HBsAg-negative mothers, the male offspring had a significantly higher HBsAg positive rate than female offspring (37.4% vs 13.8%), while in those with HBsAg-positive mothers and HBsAg-negative fathers or those with HBsAg-negative fathers and mothers, HBsAg positive rate showed no significant difference between male and female offspring. In families with familial clustering of HBV infection and poor outcomes, mother-to-child transmission is still the major route of HBV transmission, but father-to-child transmission also plays a role in HBV transmission in this special population. Positive HBsAg in fathers is associated with the increased proportion of male offspring, and father-to-son transmission of HBV is higher than father-to-daughter transmission.

Patterns of Nonrandom Mating Within and Across 11 Major Psychiatric Disorders.

Psychiatric disorders are heritable, polygenic traits, which often share risk alleles and for which nonrandom mating has been suggested. However, despite the potential etiological implications, the scale of nonrandom mating within and across major psychiatric conditions remains unclear. To quantify the nature and extent of nonrandom mating within and across a broad range of psychiatric conditions at the population level. Population-based cohort using Swedish population registers. Participants were all Swedish residents with a psychiatric diagnosis of interest (attention-deficit/hyperactivity disorder, autism spectrum disorder, schizophrenia, bipolar disorder, major depression, generalized anxiety disorder, agoraphobia, social phobia, obsessive-compulsive disorder, anorexia, or substance abuse), along with their mates. Individuals with select nonpsychiatric disorders (Crohn's disease, type 1 and type 2 diabetes mellitus, multiple sclerosis, or rheumatoid arthritis) were included for comparison. General population samples were also derived and matched 1:5 with each case proband. Inpatient and outpatient diagnostic data were derived from the Swedish National Patient Register (1973-2009), with analyses conducted between June 2014 and May 2015. Correlation in the diagnostic status of mates both within and across disorders. Conditional logistic regression was used to quantify the odds of each diagnosis in the mates of cases relative to matched population controls. Across cohorts, data corresponded to 707 263 unique case individuals, with women constituting 45.7% of the full population. Positive correlations in diagnostic status were evident between mates. Within-disorder correlations were marginally higher (range, 0.11-0.48) than cross-disorder correlations (range, 0.01-0.42). Relative to matched populations, the odds of psychiatric case probands having an affected mate were significantly elevated. Differences in the magnitude of observed relationships were apparent by disorder (odds ratio range, 0.8-11.4). The number of comorbidities in a case proband was associated with the proportion of affected mates. These relationships were not apparent or weaker in magnitude among nonpsychiatric conditions (correlation range, -0.03 to 0.17). Nonrandom mating is evident in psychiatric populations both within specific disorders and across the spectrum of psychiatric conditions. This phenomenon may hold important implications for how we understand the familial transmission of these disorders and for psychiatric genetic research.

Worker, workplace or families: What influences family focused practices in adult mental health?

Introduction Family focused practice is thought to lead to positive outcomes for all family members. However, there are multiple barriers and enablers in adult mental health services to practitioners undertaking these actions. Aim The aim of this study was to examine the relative importance of worker, workforce and family factors to predict family focused practices (FFPs) in adult mental health services. Method Three hundred and seven adult mental health workers completed a 45 items family focused practice measure of 16 family focused practices. Thesis It was found that worker skill and knowledge about family work and an ability to assess the degree of parental insight into the child's connections to other family members and the community were important predictors of FFP, along with the closely related-worker confidence. While aspects of the worker, workplace and family each contribute to FFPs, this study highlighted the importance of worker skill, knowledge and confidence as central issues for adult mental health workers. Implications for practice Study implications include the need for training in specific FFPs, the provision of time to engage with clients on parenting issues and the need 5 to ensure that there are adequate services for workers to refer family members to.

CMTX Disorder and CamKinase.

Charcot-Marie-Tooth disease is a demyelinating peripheral neuropathy and is a heterogeneous inherited disorder (40 loci have been described so far) affecting peripheral nerves. Two forms, CMT1A and CMTX, account for 60 and 15% of patients, respectively, with clear familial transmission (Boerkel et al., 2002). CMTX is caused by mutations in the GBJ1 gene encoding the synthesis of connexin 32 (Cx32, Bergoffen et al., 1993), which is a myelin protein related to PNS and CNS (Scherer et al., 1995). Cx32 is a membrane protein located in gap junctions, which forms hexameric hemichannels called connexons. However, the mechanism by which anomalies in connexin 32 affect myelination and function of PNS remains is still unclear. Here, we share our opinion that CamKinase are involved in the pathophysiology of CMTX and likely involve genomic instability caused by mutations in Gjb1.

Assessing the Validity of the Age at Onset Criterion for Diagnosing ADHD in DSM-5

Objective: Research about Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) age of onset criterion for ADHD led to increasing that criterion to 12 in Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). Although an improvement from the previous age at onset of 7, whether this new criterion is adequate to capture all cases with ADHD remains uncertain. Method: We compared three groups of adults: (a) ADHD participants who met all DSM-5 criteria for ADHD (n = 182), (b) late-onset ADHD participants who met all criteria except for later age at onset (n = 17), and (c) non-ADHD participants who did not meet criteria for ADHD (n = 117). We assessed patterns of symptoms, psychiatric comorbidity, functional impairment, familial transmission, quality of life, social adjustment, and intelligence. Results: Compared with non-ADHD participants, all ADHD groups had poorer quality of life and had more impaired social adjustment. Compared with each other, the ADHD groups had similar patterns of psychiatric comorbidity, functional impairment, familial transmission, and intelligence. Conclusion: When assessing adult ADHD, self-reported onsets of ADHD after 12 years of age may be warranted.

Understanding the covariation of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms: A population-based adult twin study.

Chronic tic disorders (TD), attention-deficit/hyperactivity-disorder (ADHD), and obsessive-compulsive disorder (OCD) frequently co-occur in clinical and epidemiological samples. Family studies have found evidence of shared familial transmission between TD and OCD, whereas the familial association between these disorders and ADHD is less clear. This study aimed to investigate to what extent liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms is caused by shared or distinct genetic or environmental influences, in a large population-representative sample of Swedish adult twins (n = 21,911). Tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms showed modest, but significant covariation. Model fitting suggested a latent liability factor underlying the three phenotypes. This common factor was relatively heritable, and explained significantly less of the variance of attention-deficit/hyperactivity symptom liability. The majority of genetic variance was specific rather than shared. The greatest proportion of total variance in liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms was attributed to specific non-shared environmental influences. Our findings suggest that the co-occurrence of tics and obsessive-compulsive symptoms, and to a lesser extent attention-deficit/hyperactivity symptoms, can be partly explained by shared etiological influences. However, these phenotypes do not appear to be alternative expressions of the same underlying genetic liability. Further research examining sub-dimensions of these phenotypes may serve to further clarify the association between these disorders and identify more genetically homogenous symptom subtypes. © 2016 Wiley Periodicals, Inc.

The possible role of chromosome X variability in hypertensive familiarity

Familiarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67–3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66–3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01–2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87–4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype.

A latent profile analysis of math achievement, numerosity, and math anxiety in twins.

Underperformance in math is a problem with increasing prevalence, complex etiology, and severe repercussions. This study examined the etiological heterogeneity of math performance in a sample of 264 pairs of 12-year-old twins assessed on measures of math achievement, numerosity and math anxiety. Latent profile analysis indicated five groupings of individuals representing different patterns of math achievement, numerosity and math anxiety, coupled with differing degrees of familial transmission. These results suggest that there may be distinct profiles of math achievement, numerosity and anxiety; particularly for students who struggle in math.

A computational method for genotype calling in family-based sequencing data.

BackgroundAs sequencing technologies can help researchers detect common and rare variants across the human genome in many individuals, it is known that jointly calling genotypes across multiple individuals based on linkage disequilibrium (LD) can facilitate the analysis of low to modest coverage sequence data. However, genotype-calling methods for family-based sequence data, particularly for complex families beyond parent-offspring trios, are still lacking.ResultsIn this study, first, we proposed an algorithm that considers both linkage disequilibrium (LD) patterns and familial transmission in nuclear and multi-generational families while retaining the computational efficiency. Second, we extended our method to incorporate external reference panels to analyze family-based sequence data with a small sample size. In simulation studies, we show that modeling multiple offspring can dramatically increase genotype calling accuracy and reduce phasing and Mendelian errors, especially at low to modest coverage. In addition, we show that using external panels can greatly facilitate genotype calling of sequencing data with a small number of individuals. We applied our method to a whole genome sequencing study of 1339 individuals at ~10X coverage from the Minnesota Center for Twin and Family Research.ConclusionsThe aggregated results show that our methods significantly outperform existing ones that ignore family constraints or LD information. We anticipate that our method will be useful for many ongoing family-based sequencing projects. We have implemented our methods efficiently in a C++ program FamLDCaller, which is available from http://www.pitt.edu/~wec47/famldcaller.html.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-0880-5) contains supplementary material, which is available to authorized users.

Czech immigrant dialects in the Northern Caucasus and Western Siberia

AbstractThe article deals with essential aspects of the sociolinguistic situation and, partly, the phonological and grammatical systems of Czech immigrants’ dialects spoken in Russia. One of the examined dialects is used in two villages near Novorossiysk and Anapa in the Northern Caucasus, and the other in the Middle Irtysh area of the Omsk Region. The dialects appeared as a result of different waves of Czech rural migration at the end of the 1860s and the start of the twentieth century. The primary purpose of this research is to describe the process of formation of the two dialects, their functioning within the community and their contact with the languages used outside, as well as external factors that contributed first to their survival and then to the breach of dialect transmission in families since the 1970s. In the process, the article outlines the main linguistic features of the two dialects, focusing on those that indicate the dialects’ origin and those that have been affected by the languages of their surroundings. The corpus of interviews with speakers of Czech heritage in Russia used in this article likely represents the largest data collection to date.