The Wiley-Blackwell Handbook of Childhood Social Development. Группа авторов
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To date, there have been three GWAS studies of adult antisocial behavior. Salvatore, Aliev, and colleagues (2015) conducted a case‐control study using a sample of 1,379 participants in which the cases met criteria for alcohol dependence. The results indicated that more significantly associated genes were over‐represented in seven gene sets, and most were immune related. The most highly associated SNP was located in the ABCB1 gene, which is robustly expressed in the brain. Another study of a broad spectrum of antisocial behavior by Tielbeek and colleagues (2017) is the largest study of this phenotype conducted up to date, with combined data from five large population‐based cohorts and three target samples. The discovery samples comprised 16,400 individuals, whereas the target samples consisted of 9,381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7–56.1 years). Three promising loci with sex‐discordant associations were found: two in females, (chromosome 1: rs2764450, chromosome 11: rs11215217) and one in males (chromosome X, rs41456347) (Tielbeek et al., 2017). Finally, a study using a family‐based GWAS approach in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7568; African ancestry = 3274) did not discover any robust genome‐wide significant signals for any of the externalizing scores derived from criterion counts of five DSM disorders (alcohol dependence, alcohol abuse, illicit drug dependence, illicit drug abuse, and either antisocial personality disorder or conduct disorder) (Barr et al., 2020).
Overall, very few associations of genetic variants with antisocial behavior have been found so far and they need replication in independent studies. Similar to candidate gene association studies, possible reasons for the lack of robust findings in GWAS include: a low statistical power associated with small sample sizes; phenotypic heterogeneity; and sample differences (age, ethnicity) (Manolio et al., 2009). In addition, technical characteristics of genotyping methods may also contribute to nonreplication. Most GWASs have focused on common, rather than rare, genetic variants, such as common SNPs. However, rare deletions and insertions in the genome can play an important role. For example, effects of rare copy number variants (CNVs) have been shown in studies of autism spectrum disorder (Levy et al., 2011) and ADHD (Elia et al., 2012; Hawi et al., 2015). More recently, high‐throughput sequencing methods have been employed to study rare point mutations across the whole genome (Iossifov et al., 2014; Yuen et al., 2015). It is increasingly evident that the genetic architecture of psychological traits involves both common and rare variants and their impact on hundreds of genes. Establishing the sequence of all three billion nucleotide base pairs of an individual is becoming progressively cheaper (the cost of sequencing a genome is approximately $1,000; www.genome.gov/sequencingcosts). In the near future, it will be possible to sequence the whole genome of all people. This development may lead to unprecedented opportunities for scientific discoveries and for applying these discoveries for the benefit of all people.
Although most SNPs have very small effects on phenotypes, tens and hundreds of individual SNPs can be aggregated into SNP composites. Such a composite is called a polygenic (risk) score (PS or PRS), or polygenic index. Polygenic scores can be used to determine a degree of genetic probability for developing a particular trait or a disorder. For example, (Salvatore, Aliev et al., 2015) reported that polygenic scores for externalizing disorders – based on SNP weights derived from GWAS results in 1,249 adults – predicted externalizing disorders, subclinical externalizing behavior, and impulsivity‐related traits among 248 adolescents and 207 young adults.
Polygenic scores can also be used for identifying genetic overlaps between different traits or disorders. Tielbeek and colleagues (2017) detected a significant inverse genetic correlation of polygenic scores for antisocial behavior with educational attainment (r = ‐0.52), suggesting common genetic mechanisms between these two phenotypes. Interestingly, a different study tested how polygenic scores showing low educational attainment were related to the development of antisocial behavior from childhood through adulthood using data from two population‐based birth cohort studies, the Dunedin birth cohort from New Zealand and the E‐Risk study from the United Kingdom (Wertz et al., 2018). They found that the education‐related polygenic score predicted risk of a criminal record with modest effect sizes. Moreover, polygenic risk manifested during primary schooling in lower cognitive abilities, lower self‐control, academic difficulties, and truancy, and it was associated with a life‐course‐persistent pattern of antisocial behavior that has an onset in childhood and persists into adulthood.
In addition to molecular genetic methods, family‐based studies can also be implemented to study genetic influences on complex psychological traits. These studies are based on comparisons of family members with a different degree of genetic relatedness. Two types of family‐based studies widely used in behavioral genetic research are twin studies and adoption studies.
Twin studies
Twin studies use comparisons on a particular trait between monozygotic (MZ, identical) and dizygotic (DZ, fraternal) twins. Because MZ twins are 100% genetically similar, whereas DZ twins share on average only 50% of their segregated DNA (the part of DNA that varies between people), the twin method allows for estimation of heritability – the proportion of individual differences of a particular trait in a specific population explained by genetic differences. Heritability is estimated as double the difference between MZ and DZ twin correlations for a particular trait. By comparing MZ and DZ twins, we can also estimate the effects of environmental influences (as explained in the section “The Role of Environments Factors in Social Development”).
Twin studies have been established in many countries across the world, and some of these studies have been following twins for many years, even decades. These data allow for longitudinal investigations of genetic and environmental effects. For example, in the United Kingdom, the Twins Early Development Study (TEDS), is one of the most impressive examples of a developmental twin study – a representative longitudinal study of more than 10,000 twin pairs followed for more than 20 years, from birth to date. The main aim of this project is the study of different aspects of psychological development, such as cognitive abilities, behavior, and learning abilities and disabilities (Haworth et al., 2013; Rimfeld et al., 2019). Other large‐scale twin studies also exist in the United States (the Colorado Twin Registry), Canada (the Quebec Newborn Twin Study), Denmark (the Danish Twin Registry), Netherlands (the Young Netherlands Twin Register), South Korea (the South Korean Twin Registry), and Russia (the Russian School Twin Register). For more information, see the online resource: Meta‐Analysis of twin correlations and heritability (http://match.ctglab.nl/#/home).
Twin studies of antisocial behavior have shown that genetic factors account for approximately 45% of the variance in this trait in childhood and adolescence (Burt et al., 2007). Antisocial behavior is a heterogeneous phenotype; some authors differentiate an aggressive disorder that manifests itself in early periods (childhood) and a delinquent disorder that manifests itself in later periods (adolescence) (Moffitt, 1993). Ratings of aggression correlate with a diagnosis of oppositional disorder, whereas scores on the delinquent behavior scale correlate with a diagnosis of conduct disorder (Hudziak et al., 2004). It is possible that the two types of antisocial behavior disorders have different etiologies. Genetic factors account for up to 75% of variance in aggression, and these genetic influences are shown to be stable across ages (Bartels et al., 2004; Burt & Neiderhiser, 2009; Van Beijsterveldt et al., 2003).
An analysis of a large, multinational dataset (42,468 twin pairs from five European twin cohorts) found a high level of overall heritability of aggression in children (~60%), with heritability estimates of ~64% in boys and ~58% in girls. Interestingly, the study also reported sibling interaction effects in the opposite‐sex twin pairs: an aggressive female had a positive effect on male co‐twin aggression, whereas more aggression in males had a negative influence on a female co‐twin (Luningham et al., 2020).
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