Peter M. Visscher
University of Queensland
Publications 686
Computational advances have fostered the development of new methods and tools to integrate gene expression and functional evidence into human-genetic association analyses. Integrative functional genomics analysis for altered response to alcohol in mice provided the first evidence that multi-species analysis tools, such as GeneWeaver, can identify or confirm novel alcohol related loci. The present study describes an integrative framework to investigate how highly connected genes linked by their a...
Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identified 143 independent loci in 112 1-Mb regions providing new insights into the physiology of vitamin D and implicating genes involved in (a) lipid and lipoprotein metabolism, (b) dermal tissue properties, and (c) the sulphonation and glucuronidation of 25OHD. Mendelian randomization models found no rob...
#1Loic Yengo (UQ: University of Queensland)H-Index: 43
#2Naomi R. Wray (UQ: University of Queensland)H-Index: 79
Last.Peter M. Visscher (UQ: University of Queensland)H-Index: 109
view all 3 authors...
In most human societies, there are taboos and laws banning mating between first- and second-degree relatives, but actual prevalence and effects on health and fitness are poorly quantified. Here, we leverage a large observational study of ~450,000 participants of European ancestry from the UK Biobank (UKB) to quantify extreme inbreeding (EI) and its consequences. We use genotyped SNPs to detect large runs of homozygosity (ROH) and call EI when >10% of an individual’s genome comprise ROHs. We esti...
1 CitationsSource
#1Fengchun Zhang (UQ: University of Queensland)H-Index: 13
#2Wenhan Chen (UQ: University of Queensland)H-Index: 2
Last.Jian Yang (WMU: Wenzhou Medical College)H-Index: 97
view all 11 authors...
The rapid increase of omic data has greatly facilitated the investigation of associations between omic profiles such as DNA methylation (DNAm) and complex traits in large cohorts. Here, we propose a mixed-linear-model-based method called MOMENT that tests for association between a DNAm probe and trait with all other distal probes fitted in multiple random-effect components to account for unobserved confounders. We demonstrate by simulations that MOMENT shows a lower false positive rate and more ...
4 CitationsSource
#1Yongjie Yang (BCM: Baylor College of Medicine)H-Index: 9
#2Agatha A. van der Klaauw (University of Cambridge)H-Index: 16
Last.Weihua ZhangH-Index: 63
view all 265 authors...
Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozy...
12 CitationsSource
#1Qian Zhang (UQ: University of Queensland)H-Index: 50
#2Costanza L. Vallerga (UQ: University of Queensland)H-Index: 6
Last.Peter M. Visscher (UQ: University of Queensland)H-Index: 109
view all 33 authors...
DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed ‘epigenetic clocks’. The deviation of predicted age from the actual age (‘age acceleration residual’, AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association. In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 samples (13,402 from blood and 259...
1 CitationsSource
Summary Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated ...
7 CitationsSource
#1Regina H Reynolds (UCL: University College London)H-Index: 3
#2Juan A. Botía (UCL: University College London)H-Index: 19
Last.John V. PearsonH-Index: 48
view all 167 authors...
Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomi...
7 CitationsSource
#1Darina Czamara (MPG: Max Planck Society)H-Index: 5
#2Gökcen Eraslan (TUM: Technische Universität München)H-Index: 4
Last.Elisabeth B. Binder (MPG: Max Planck Society)H-Index: 75
view all 229 authors...
Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overal...
2 CitationsSource
#1Robert F. Hillary (Edin.: University of Edinburgh)H-Index: 3
#2Daniel L. McCartney (Edin.: University of Edinburgh)H-Index: 5
Last.Riccardo E. Marioni (Edin.: University of Edinburgh)H-Index: 40
view all 15 authors...
Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. Therefore, we conduct genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750 healthy older adults). We identify 41 independent genome-wide significant (P < 5.4 × 10−10) loci for 33 ...