Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

Abstract

We obtained evidence from a large study in Dutch twins (N=8387) and siblings (N=2295) that variation in loneliness has a genetic component. The heritability estimate for loneliness, which was assessed as an ordinal trait, was 40% and did not differ between males and females. There were 682 sibling pairs with genotypic (around 400 microsatellite markers) data. We combined phenotypic and genotypic data to carry out a genome scan to localize QTLs for loneliness. One region on chromosome 12q23.3-24.3, showed near suggestive linkage. Genetic association tests within this region revealed significant association ( p-value 0.009) with one of the alleles of marker D12S79 and with one of the alleles of neighbouring marker D12S395 ( p-value 0.043). We review evidence for linkage in this region for psychiatric disorders and discuss our findings within this context.

Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation

“…This latter result is especially interesting in light of the behavioral research showing that loneliness and psychiatric illness are related in other contexts (Cacioppo et al, 2015c), and provides novel evidence that such associations may reflect genetic as well as environmental influences. Prior behavioral genetic studies have used adoption designs (McGuire and Clifford, 2000), twin designs (Boomsma et al, 2005;Waaktaar and Torgersen, 2012), a family-based design including nontwin siblings (Boomsma et al, 2006), and an extended twin designs to include the partners and parents of twins (Distel et al, 2010) to estimate the heritability of loneliness in a variety of populations (Goossens et al, 2015). The heritability estimates across these various designs have ranged from 37 to 55%.…”

“…The heritability of loneliness has been documented in twin and other studies using both children (Bartels et al, 2008;McGuire and Clifford, 2000) and adults (Boomsma et al, 2005(Boomsma et al, , 2006(Boomsma et al, , 2007. For instance, in an early longitudinal study of 8387 young adult and adult Dutch twins who participated in longitudinal surveys, Boomsma et al, (2005) analyzed variations in loneliness with genetic structural equation models.…”

“…Boomsma et al (2005) found no evidence for sex or age differences in heritability. Subsequent twin studies have yielded heritability estimates ranging from 37 to 55% (Boomsma et al, 2005(Boomsma et al, , 2006Distel et al, 2010;McGuire and Clifford, 2000;Waaktaar and Torgersen, 2012). Candidate gene studies for loneliness have concentrated primarily on systems related to monoamine neurotransmitters (eg, dopamine, serotonin) and other signaling pathways associated with human attachment (eg, oxytocin) (Goossens et al, 2015).…”

Alone in the Crowd: The Structure and Spread of Loneliness in a Large Social Network

“…Adoption and twin studies indicate that loneliness has a sizable heritable component in children (Bartels, Cacioppo, Hudziak, & Boomsma, 2008;Mcguire & Clifford, 2000) and in adults (Boomsma, Cacioppo, Slagboom, & Posthuma, 2006;Boomsma, Willemsen, Dolan, Hawkley, & Cacioppo, 2005;Boomsma, Cacioppo, Muthen, Asparouhov, & Clark, 2007).…”

Van generatie op generatie : Gelijkenis tussen ouders en kinderen

“…Hierbij wordt gekeken of familieleden die wat betreft hun mate van eenzaamheid veel op elkaar lijken ook op bepaalde plekken op het genoom meer DNA-varianten met elkaar delen. De eerste koppelingsstudie voor eenzaamheid (Boomsma, Cacioppo, Slagboom, & Posthuma, 2006) werd uitgevoerd op de eenzaamheidsdata van het NTR. Bij een aantal NTR-deelnemers zijn DNA-monsters verzameld (Heijmans, Beekman, Putter, Lakenberg, Van der Wijk, Whitfield, e.a., & Slagboom, 2005;Boomsma, Beem, Van den Berg, Dolan, Koopmans, Vink, e.a., 2000).…”