Emergenesis: Genetic traits that may not run in familes.

Traits that are influenced by a configuration--rather than by a simple sum-- of polymorphic genes may not be seen to be genetic unless one studies monozygotic twins (who share all their genes and thus all gene configurations) because such “emergenic” traits will tend not to run in families. Personal idiosyncrasies that have been found to be surprisingly concordant among MZ twins separated in infancy and reared apart may be emergenic traits. More speculatively, important human traits like leadership, genius in its many manfestations, being an eflective therapist or parent, as well as certain psychopathological syndromes, may also be emergenic. These ideas re-emphasize the importance of the role played in human aflairs by genetic variation

Risk of Suicide Attempt in Adopted and Nonadopted Offspring

OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadoptees were ascertained from Minnesota birth records. Outcome measures were attempted suicide, reported by parent or offspring, and factors known to be associated with suicidal behavior including psychiatric disorder symptoms, personality traits, family environment, and academic disengagement. RESULTS: The odds of a reported suicide attempt were ∼4 times greater in adoptees compared with nonadoptees (odds ratio: 4.23). After adjustment for factors associated with suicidal behavior, the odds of reporting a suicide attempt were reduced but remained significantly elevated (odds ratio: 3.70). CONCLUSIONS: The odds for reported suicide attempt are elevated in individuals who are adopted relative to those who are not adopted. The relationship between adoption status and suicide attempt is partially mediated by factors known to be associated with suicidal behavior. Continued study of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults

Relationship between personality change and the onset and course of alcohol dependence in young adulthood

Aims  To examine the reciprocal effects between the onset and course of alcohol use disorder (AUD) and normative changes in personality traits of behavioral disinhibition and negative emotionality during the transition between adolescence and young adulthood. Design  Longitudinal–epidemiological study assessing AUD and personality at ages 17 and 24 years. Setting  Participants were recruited from the community and took part in a day‐long, in‐person assessment. Participants  Male ( n  = 1161) and female ( n  = 1022) twins participating in the Minnesota Twin Family Study. Measurements  The effects of onset (adolescent versus young adult) and course (persistent versus desistent) of AUD on change in personality traits of behavioral disinhibition and negative emotionality from ages 17 to 24 years. Findings  Onset and course of AUD moderated personality change from ages 17 to 24 years. Adolescent onset AUD was associated with greater decreases in behavioral disinhibition. Those with an adolescent onset and persistent course failed to exhibit normative declines in negative emotionality. Desistence was associated with a ‘recovery’ towards psychological maturity in young adulthood, while persistence was associated with continued personality dysfunction. Personality traits at age 11 predicted onset and course of AUD, indicating personality differences were not due to active substance abuse. Conclusions  Personality differences present prior to initiation of alcohol use increase risk for alcohol use disorder, but the course of alcohol use disorder affects the rate of personality change during emerging adulthood. Examining the reciprocal effects of personality and alcohol use disorder within a developmental context is necessary to improve understanding for theory and intervention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90257/1/j.1360-0443.2011.03617.x.pd

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

Background: As 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. Results: In 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. Conclusions: The 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

Codevelopment Between Key Personality Traits and Alcohol Use Disorder From Adolescence Through Young Adulthood

ObjectivePersonality traits related to negative emotionality and low constraint are strong correlates of alcohol use disorder (AUD), but few studies have evaluated the prospective interplay between these traits and AUD symptoms from adolescence to young adulthood.MethodThe Minnesota Twin Family Study (N = 2,769) was used to examine the developmental interplay between AUD symptoms and three personality measures of constraint, negative emotionality, and aggressive undercontrol from ages 17 to 29.ResultsResults from random‐intercept, cross‐lagged panel models showed that low constraint and aggressive undercontrol predicted subsequent rank‐order increases in AUD symptoms from ages 17 to 24. AUD symptoms did not predict rank‐order change in these traits from ages 17 to 24. There was support for both cross‐effects from ages 24 to 29. Biometric analysis of the twin data showed genetic influences accounted for most of the phenotypic correlations over time.ConclusionResults are consistent with the notion that personality traits related to low constraint and aggressive undercontrol are important vulnerability/predisposition factors for the development of early adult AUD. In later young adulthood, there is more evidence for the simultaneous codevelopment of personality and AUD. Implications are addressed with attention to personality‐based risk assessments and targeted AUD prevention approaches.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142935/1/jopy12311.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142935/2/jopy12311_am.pd

Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes

We mapped ∼85,000 rare nonsynonymous exonic single nucleotide polymorphisms ( SNPs ) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG , P 300 amplitude, electrodermal activity, affect‐modulated startle eye blink. Nonsynonymous SNPs are predicted to directly change or disrupt proteins encoded by genes and are expected to have significant biological consequences. Most such variants are rare, and new technologies can efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare ( MAF  < .05), and nonsynonymous. Single variant association tests identified a SNP in the PARD 3 gene associated with theta resting EEG power. The sequence kernel association test, a gene‐based test, identified a gene PNPLA 7 associated with pleasant difference startle, the difference in startle magnitude between pleasant and neutral images. No other single nonsynonymous variant, or gene‐based group of variants, was strongly associated with any endophenotype.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109617/1/psyp12349.pd

Gene-environment interplay in depressive symptoms:Moderation by age, sex, and physical illness

BackgroundNumerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness.MethodThe analysis sample included 24 436 twins aged 40–90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms.ResultsWomen reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2s.d.above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness.ConclusionsFindings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.</jats:sec

Narrowing the Boundaries of the Genetic Architecture of Schizophrenia

Genetic architecture of a disease comprises the number, frequency, and effect sizes of genetic risk alleles and the way in which they combine together. Before the genomic revolution, the only clue to underlying genetic architecture of schizophrenia came from the recurrence risks to relatives and the segregation patterns within families. From these clues, very simple genetic architectures could be rejected, but many architectures were consistent with the observed family data. The new era of genome-wide association studies can provide further clues to the genetic architecture of schizophrenia. We explore models of genetic architecture by description rather than the mathematics that underpins them. We conclude that the new genome-wide data allow us to narrow the boundaries on the models of genetic architecture that are consistent with the observed data. A genetic architecture of many common variants of moderate (relative risk > approximately 1.2) can be excluded, yet there is evidence that current generation genome-wide chips do tag an important proportion of the genetic variation for schizophrenia and that the underlying causal variants will include common variants of small effect as well as rarer variants of larger effect. Together, these observations imply that the total number of genetic variants is very large—of the order of thousands. The first generation of studies have generated hypotheses that should be testable in the near future and will further narrow the boundaries on genetic architectures that are consistent with empirical data