Biomedical subjects

Daniel F Levey

Publications and source records attributed to Daniel F Levey.

3 recordsLinked to original sources

PubMed2026

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗

PubMed2024

Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations.

Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.

Humans↗

PubMed2024

Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis.

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS. METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression. RESULTS: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. INTERPRETATION: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Humans↗