Biology subjects

Niedzwiedz, C. L.

Publications and source records attributed to Niedzwiedz, C. L..

3 recordsLinked to original sources

bioRxiv2022

A Genome-Wide Association Analysis of Happiness: Consistent Genetic Effects Across the Lifespan and Across Genetic Ancestries in Multiple Cohorts.

We present a genome-wide association study of a general happiness measure in 118,851 participants from the UK Biobank. Using BOLT-LMM, we identify 3 significant loci with a heritability estimate of 0.8%. Linkage disequilibrium score regression was performed on the big five personality traits finding significant associations with lower neuroticism and higher extraversion and conscientiousness. Using a novel approach, we construct LDpred-inf polygenic risk scores in the Adolescent Brain Cognitive Development (ABCD) cohort and the Add Health cohort. We detected nominally significant associations with several well-being measures in ABCD and significant correlations with a happiness measure in Add Health. Additionally, we tested for associations with several brain regions in a white British subsample of UK Biobank finding significant associations with several brain structure and integrity phenotypes. We demonstrated a genetic basis for general happiness level and brain structure that appears to remain consistent throughout the lifespan and across multiple ancestral backgrounds. Author summaryAt the genetic level, there has been little investigation into whether people may have a baseline happiness level which varies from person to person. Here we perform a genetic analysis in the UK Biobank to identify three genetic loci that associate with general happiness level and preform genetic correlations of our results with the Big Five personality traits, identifying significant correlations with neuroticism, conscientiousness and extraversion. We use the resulting summary statistics to create LDpred-inf polygenic risk scores in UK biobank identifying several brain metrics and regions associate with genetic loading for general happiness level. We also use a novel method to create LDpred-inf polygenic risk scores in two other cohorts, ABCD and Add Health. We found significant correlations with an independent happiness measure in Add Health and nominally significant correlations with several well-being measures in ABCD in both those of European Ancestry and all other ancestries found in these cohorts. We also attempted to replicate our UK Biobank MRi finding in ABCD. We conclude there is evidence that individuals have a general happiness level that is in part genetic which spans across age and ancestry.

genetics↗

bioRxiv2018

Novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.

AbstractBackground: Suicide is a major issue for global public health. Suicidality describes a broad clinical spectrum of thoughts and behaviours, some of which are common in the general population.\n\nMethods: UK Biobank recruited [~]0{middle dot}5 million middle age individuals from the UK, of whom 157,000 completed an assessment of suicidality. Mutually exclusive groups were assessed in an ordinal genome-wide association study of suicidality: no suicidality controls (N=83,557); thoughts that life was not worth living (N=21,063); ever contemplated self-harm (N=13,038); an act of deliberate self-harm in the past (N=2,498); and a previous suicide attempt (N=2,666). Linkage of UK Biobank to death certification records identified a small sub-group of completed suicide (N=137).\n\nOutcomes: We identified three novel genome-wide significant loci for suicidality (on Chromosomes 9, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0{middle dot}81). Higher polygenic risk scores for suicidality were associated with increased risk of completed suicide relative to controls in an independent sub-group (N=137 vs N=5,330, OR 1{middle dot}23, 95%CI 1{middle dot}06 to 1{middle dot}41, p=0.03). Rs598046-G (chromosome 11) demonstrated a similar effect size and direction (p=0{middle dot}05) within a Danish suicidality study.\n\nInterpretation: These findings have significant implications for our understanding of genetic vulnerability to suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level.\n\nFunding: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217).

genetics↗

bioRxiv2018

Genome-wide association study of circadian rhythmicity in 71 500 UK Biobank participants and polygenic association with mood instability

BackgroundCircadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder.\n\nMethodsWe conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of circadian rhythmicity derived from the accelerometer data of 71 500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes.\n\nOutcomesTwo independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0{middle dot}05: OR=1{middle dot}02, 95% CI=1{middle dot}01-1{middle dot}02, p=9{middle dot}6x10-5), and with major depressive disorder (at PRS threshold 0{middle dot}1: OR=1{middle dot}03, 95% CI=1{middle dot}01-1{middle dot}05, p=0{middle dot}025) and neuroticism (at PRS threshold 0{middle dot}5: Beta=0{middle dot}02, 95% CI=0{middle dot}007-0{middle dot}04, p=0{middle dot}021).\n\nInterpretationOverall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism.

genomics↗