Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness

Abstract

<jats:title>Abstract</jats:title> <jats:p>Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.</jats:p>

Prominent health problems, socioeconomic deprivation, and higher brain age in lonely and isolated individuals: A population-based study

“…Genome-wide association studies indicate that a genetic predisposition for loneliness is associated with increased susceptibility to both mental and physical health problems [44,45]. Although genetic correlations between loneliness and risk factors tend to align with phenotypic correlations, there has also been some divergence; while a phenotypic association between loneliness and alcohol abuse has been reported [46], a recent study found a genetic correlation between loneliness and lower alcohol intake [44] -in line with the current results. This finding may be linked to a genetic association between loneliness and socioeconomic status [44], which could possibly be reflected in the higher deprivation index scores and lower income observed among lonely individuals in the current study.…”

High prevalence and adverse health effects of loneliness in community-dwelling adults across the lifespan: role of wisdom as a protective factor

“…Wisdom may be a unique protective factor against loneliness. Intriguingly, recent genetics work has reported an association between loneliness and genes expressed in the prefrontal and anterior cingulate cortices (Abedellaoui et al, 2018) areas that are also related to components of wisdom (Meeks and Jeste, 2009).…”

Diverse phenotypic measurements of wellbeing: Heritability, temporal stability and the variance explained by polygenic scores

“…PHF2 is essential for proliferation of progenitors during early neurogenesis, 38 and mutations in this gene have been found in patients with autism spectrum disorder 39 . Previous GWAS have shown that variants within this gene are significantly associated with behavioral traits including neuroticism, 40 depressed affect 41 and loneliness 42,43 …”