Simultaneous Selection of Multiple Important Single Nucleotide Polymorphisms in Familial Genome Wide Association Studies Data

We propose a resampling-based fast variable selection technique for selecting important Single Nucleotide Polymorphisms (SNP) in multi-marker mixed effect models used in twin studies. Due to computational complexity, current practice includes testing the effect of one SNP at a time, commonly termed as `single SNP association analysis'. Joint modeling of genetic variants within a gene or pathway may have better power to detect the relevant genetic variants, hence we adapt our recently proposed framework of $e$-values to address this. In this paper, we propose a computationally efficient approach for single SNP detection in families while utilizing information on multiple SNPs simultaneously. We achieve this through improvements in two aspects. First, unlike other model selection techniques, our method only requires training a model with all possible predictors. Second, we utilize a fast and scalable bootstrap procedure that only requires Monte-Carlo sampling to obtain bootstrapped copies of the estimated vector of coefficients. Using this bootstrap sample, we obtain the $e$-value for each SNP, and select SNPs having $e$-values below a threshold. We illustrate through numerical studies that our method is more effective in detecting SNPs associated with a trait than either single-marker analysis using family data or model selection methods that ignore the familial dependency structure. We also use the $e$-values to perform gene-level analysis in nuclear families and detect several SNPs that have been implicated to be associated with alcohol consumption

The Determinants of Leadership: The Role of Genetic, Personality, and Cognitive Factors

A sample of 646 male twins (331 monozygotic or identical, 315 dizygotic or fraternal) completed a survey indicating their leadership role occupancy in work settings. Data on these individuals were also available for personality and cognitive variables. As predicted, two personality variables (Social Potency and Achievement) and a cognitive variable (a vocabulary test) were significantly correlated with the leadership variable. Subsequently, univariate and multivariate genetic analyses showed that a substantial portion of this leadership variance was accounted for by genetic factors (39 percent) while non-shared (or non-common) environmental factors accounted for the remaining variance in this leadership variable. Genetic influences were shown for the personality and cognitive factors as well. Finally, results indicated that the genetic influences for the leadership factor were substantially associated with or common with the genetic factors influencing the personality factors, but not with the cognitive variable.

Changes in Genetic and Environmental Influences on the Development of Nicotine Dependence and Major Depressive Disorder from Middle Adolescence to Early Adulthood

This longitudinal study used a representative community sample of same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) to study longitudinal changes in genetic and environmental influences on nicotine dependence (NicD) symptoms and major depressive disorder (MDD) symptoms and the longitudinal relationships between NicD and MDD symptoms at three relatively discrete ages spanning middle adolescence to early adulthood (ages 15, 18, and 21). Clinical interviews were used to assess NicD and MDD symptoms lifetime at age 15 and during the previous 3 years at the two subsequent assessments. Biometric models revealed similar patterns of findings for NicD and MDD. Heritability increased with age, particularly between ages 15 and 18. Shared environmental influences were small, and the proportion of variance attributed to shared environmental influences decreased with age. Nonshared environmental influences were moderate to large in magnitude and were entirely age specific. Both NicD and MDD symptoms showed considerable stability from age 15 to 21, and at each age those with one disorder showed elevated rates of the other. However, a cross-lagged model revealed no longitudinal predictive relationships between MDD symptoms and NicD symptoms after accounting for stability of symptoms within disorders. In summary, the transition between middle and late adolescence is a critical period for developmental shifts in the magnitudes of genetic and environmental influences on both MDD and NicD symptoms. Despite similarities in the development of genetic and environmental influences for the two phenotypes, the association between NicD and MDD reflects concurrent covariation rather than one phenotype being an antecedent influence on the subsequent development of the other

Genetic amplification and the individuation of the parent-child relationship across adolescence

BACKGROUND: Many psychological traits become increasingly influenced by genetic factors throughout development, including several which might intuitively be seen as purely environmental characteristics. One such trait is the parent-child relationship, which is associated with a variety of socially significant outcomes, including mental health and criminal behavior. Genetic factors have been shown to partially underlie some of these associations, but the changing role of genetic influence over time remains poorly understood. METHOD: Over 1,000 participants in a longitudinal twin study were assessed at three points across adolescence with a self-report measure regarding the levels of warmth and conflict in their relationships with their parents. These reports were analyzed with a biometric growth curve model to identify changes in genetic and environmental influences over time. RESULTS: Genetic influence on the child-reported relationship with parent increased throughout adolescence, while the relationship’s quality deteriorated. The increase in genetic influence resulted primarily from a positive relation between genetic factors responsible for the initial relationship and those involved in change in the relationship over time. In contrast, environmental factors relating to change were negatively related to those involved in the initial relationship. CONCLUSIONS: The increasing genetic influence appears due to early genetic influences having greater freedom of expression over time, while environmental circumstances were decreasingly important to variance in the parent-child relationship. We infer that the parent-child relationship may become increasingly influenced by the particular characteristics of the child (many of which are genetically-influenced), gradually displacing the effects of parental or societal ideas of child-rearing

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