ORCID Profile
0000-0003-3352-0603
Current Organisation
Gold Coast University Hospital
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Publisher: Proceedings of the National Academy of Sciences
Date: 08-09-2014
Abstract: We identify several common genetic variants associated with cognitive performance using a two-stage approach: we conduct a genome-wide association study of educational attainment to generate a set of candidates, and then we estimate the association of these variants with cognitive performance. In older Americans, we find that these variants are jointly associated with cognitive health. Bioinformatics analyses implicate a set of genes that is associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. In addition to the substantive contribution, this work also serves to show a proxy-phenotype approach to discovering common genetic variants that is likely to be useful for many phenotypes of interest to social scientists (such as personality traits).
Publisher: Cambridge University Press (CUP)
Date: 03-12-2015
DOI: 10.1017/THG.2014.70
Abstract: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population s le may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years standard deviation 0.25). Plasma cytokine measures were available for 400 in iduals (85 MZ, 115 DZ pairs), dried blood spot s le vitamin D measures were available for 378 in iduals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger s le sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Springer Science and Business Media LLC
Date: 29-11-2016
DOI: 10.1038/MP.2016.213
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/JCPP.12295
Abstract: Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. S le sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Increasing the s le size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as s le sizes increase and as s le resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2010
Publisher: Springer Science and Business Media LLC
Date: 08-09-2016
DOI: 10.1038/SREP32894
Abstract: We propose a method (fastBAT) that performs a fast set-based association analysis for human complex traits using summary-level data from genome-wide association studies (GWAS) and linkage disequilibrium (LD) data from a reference s le with in idual-level genotypes. We demonstrate using simulations and analyses of real datasets that fastBAT is more accurate and orders of magnitude faster than the prevailing methods. Using fastBAT, we analyze summary data from the latest meta-analyses of GWAS on 150,064–339,224 in iduals for height, body mass index (BMI), and schizophrenia. We identify 6 novel gene loci for height, 2 for BMI, and 3 for schizophrenia at P fastBAT 5 × 10 −8 . The gain of power is due to multiple small independent association signals at these loci (e.g. the THRB and FOXP1 loci for schizophrenia). The method is general and can be applied to GWAS data for all complex traits and diseases in humans and to such data in other species.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2015
DOI: 10.1038/NG.3390
Publisher: Wiley
Date: 24-07-2013
Publisher: Springer Science and Business Media LLC
Date: 29-11-2009
Publisher: Cambridge University Press (CUP)
Date: 08-10-2014
DOI: 10.1017/S2045796014000584
Abstract: G × E in psychiatry may explain why environmental risk factors have big impact in some in iduals but not in others, and conversely why relatives that are genetically at risk for disease do not all develop disease. Here we discuss two novel methods that use an aggregate genome-wide measure of genetic risk to detect G × E and estimate its effect in the population using data currently available and data we anticipate will be available in the near future. The first method exploits summary statistics from large-scale genome-wide association studies ignorant of the environmental conditions and detects G × E in an out-of-s le risk-profiling framework. The second method relies on larger s les and is based on a mixed linear model framework. It estimates variance explained directly from single nucleotide polymorphisms and environmental measures. Both methods have great potential to improve public health interventions focusing on risk-based screening that is informed by both genetic and environmental risk factors.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2014
DOI: 10.1038/NG.3097
Publisher: Public Library of Science (PLoS)
Date: 10-04-2014
Publisher: Wiley
Date: 24-05-2012
DOI: 10.1002/AJMG.B.32072
Publisher: Elsevier BV
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 04-10-2011
Publisher: Elsevier BV
Date: 2016
Publisher: Wiley
Date: 18-08-2015
DOI: 10.1002/AJMG.B.32352
Abstract: Autistic traits are characterized by social and communication problems, restricted, repetitive and stereotyped patterns of behavior, interests and activities. The relation between autistic traits and personality characteristics is largely unknown. This study focused on the relation between five specific autistic traits measured with the abridged version of the Autism Spectrum Quotient ("social problems," "preference for routine," "attentional switching difficulties," "imagination impairments," "fascination for numbers and patterns") and Experience Seeking (ES) in a general population s le of adults, and subsequently investigated the genetic and environmental etiology between these traits. Self-reported data on autistic traits and ES were collected in a population s le (n = 559) of unrelated in iduals, and in a population based family s le of twins and siblings (n = 560). Phenotypic, genetic and environmental associations between traits were examined in a bivariate model, accounting for sex and age differences. Phenotypically, ES correlated significantly with "preference for routine" and "imagination impairments" in both s les but was unrelated to the other autistic traits. Genetic analyses in the family s le revealed that the association between ES and "preference for routine" and "imagination impairments" could largely be explained by a shared genetic factor (89% and 70%, respectively). Our analyses demonstrated at a phenotypic and genetic level an inverse relationship between ES and specific autistic traits in adults. ES is associated with risk taking behavior such as substance abuse, antisocial behavior and financial problems. Future research could investigate whether autistic traits, in particular strong routine preference and impaired imagination skills, serve as protective factors for such risky behaviors. © 2015 Wiley Periodicals, Inc.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2009
Publisher: Wiley
Date: 15-11-2016
DOI: 10.1002/AJMG.B.32512
Publisher: Springer Science and Business Media LLC
Date: 10-02-2021
DOI: 10.1186/S13229-020-00407-5
Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 in iduals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed ( n = 871) or suspected ( n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European ( n = 1,964 European in iduals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. The ASD ( p = 6.1e−13), sibling ( p = 4.9e−3) and unrelated ( p = 3.0e−3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height—a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children ( r = 0.24, p = 2.1e−3) and parents ( r = 0.17, p = 8.0e−7 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group ( r = 0.13, p = 1.9e−3 1.3% of variance). In the CNV analysis, we identified 13 in iduals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).
Publisher: Springer Science and Business Media LLC
Date: 11-05-2016
DOI: 10.1038/NATURE17671
Publisher: SAGE Publications
Date: 06-10-2014
Abstract: A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R 2 ≈ 0.02%), reached genome-wide significance ( p 5 × 10 −8 ) in a large discovery s le and were replicated in an independent s le ( p .05). The study also reported associations between educational attainment and indices of SNPs called “polygenic scores.” In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large ( N = 34,428) independent s le. We also found that the scores remained predictive ( R 2 ≈ 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of in idual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies.
Publisher: SAGE Publications
Date: 20-11-2014
Abstract: The hemodynamic response function (HRF) describes the local response of brain vasculature to functional activation. Accurate HRF modeling enables the investigation of cerebral blood flow regulation and improves our ability to interpret fMRI results. Block designs have been used extensively as fMRI paradigms because detection power is maximized however, block designs are not optimal for HRF parameter estimation. Here we assessed the utility of block design fMRI data for HRF modeling. The trueness (relative deviation), precision (relative uncertainty), and identifiability (goodness-of-fit) of different HRF models were examined and test–retest reproducibility of HRF parameter estimates was assessed using computer simulations and fMRI data from 82 healthy young adult twins acquired on two occasions 3 to 4 months apart. The effects of systematically varying attributes of the block design paradigm were also examined. In our comparison of five HRF models, the model comprising the sum of two gamma functions with six free parameters had greatest parameter accuracy and identifiability. Hemodynamic response function height and time to peak were highly reproducible between studies and width was moderately reproducible but the reproducibility of onset time was low. This study established the feasibility and test–retest reliability of estimating HRF parameters using data from block design fMRI studies.
Publisher: Oxford University Press (OUP)
Date: 18-08-2015
DOI: 10.1093/IJE/DYV136
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JSBMB.2015.09.018
Abstract: Population-based studies have confirmed that the prevalence of vitamin D deficiency is substantial in many societies, and is of particular concern in pregnant women. Vitamin D deficiency during pregnancy is associated with a wide range of adverse maternal and offspring health outcomes. To date, studies of vitamin D deficiency during pregnancy have focused on measurements at one or two time points in isolation. We examined both midgestation and cord blood 25 hydroxyvitamin D (25OHD) concentration and explored the prevalence and correlates of vitamin D deficiency in a large ethnically erse cohort of pregnant women and their infants in the Netherlands. This study was embedded in the Generation R Study, a population-based prospective cohort from fetal life onwards in Rotterdam, The Netherlands. Using a highly sensitive tandem mass spectroscopy-based assay, we measured 25OHD in 7256 midgestation s les (mean gestation 20.6 weeks) and 5023 neonatal cord blood s les (mean gestation 40.0 weeks). Using a conservative threshold of less than 25nmol/L to define vitamin D deficiency, we examined the prevalence and socio-demographic correlates of vitamin D deficiency in mothers and infants. We also derived a measure of vitamin D deficiency based on the two time points in order to explore persistent vitamin D deficiency in mother-infant pairs. The prevalence of vitamin D deficiency at midgestation was 26%, while in neonates 46% were deficient. 21% of the mother-infant pairs had persistent vitamin D deficiency (i.e., deficient in maternal and cord s les) and an additional 29% were vitamin D deficient in one of the two s les only. Persistent vitamin D deficiency was strongly associated with non-European ancestry and spring birth. A sizeable proportion of women and their neonatal offspring in the Generation R cohort were vitamin D deficient. In light of the large body of evidence linking vitamin D deficiency with adverse health outcomes for pregnant women and their offspring, our findings indicate a large unmet need in this population. In particular, women and infants from non-European ethnic background are at high risk of vitamin D deficiency.
Publisher: Wiley
Date: 04-2010
Publisher: Elsevier BV
Date: 06-2015
Publisher: Public Library of Science (PLoS)
Date: 07-04-2014
Publisher: Cambridge University Press (CUP)
Date: 21-12-2012
DOI: 10.1017/S0033291712002863
Abstract: Attention deficit hyperactivity disorder (ADHD) symptoms and autistic traits often occur together. The pattern and etiology of co-occurrence are largely unknown, particularly in adults. This study investigated the co-occurrence between both traits in detail, and subsequently examined the etiology of the co-occurrence, using two independent adult population s les. Data on ADHD traits (Inattention and Hyperactivity/Impulsivity) were collected in a population s le (S1, n = 559) of unrelated in iduals. Data on Attention Problems (AP) were collected in a population-based family s le of twins and siblings (S2, n = 560). In both s les five dimensions of autistic traits were assessed (social skills, routine, attentional switching, imagination, patterns). Hyperactive traits (S1) did not correlate substantially with the autistic trait dimensions. For Inattention (S1) and AP (S2), the correlations with the autistic trait dimensions were low, apart from a prominent correlation with the attentional switching scale (0.47 and 0.32 respectively). Analyses in the genetically informative S2 revealed that this association could be explained by a shared genetic factor. Our findings suggest that the co-occurrence of ADHD traits and autistic traits in adults is not determined by problems with hyperactivity, social skills, imagination or routine preferences. Instead, the association between those traits is due primarily to shared attention-related problems (inattention and attentional switching capacity). As the etiology of this association is purely genetic, biological pathways involving attentional control could be a promising focus of future studies aimed at unraveling the genetic causes of these disorders.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10495
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 in iduals. Twelve loci reached genome-wide significance ( P × 10 −8 ), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14 , IGF2BP1 , PLA2G6 , CRTC1 ) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Publisher: Oxford University Press (OUP)
Date: 22-10-2015
DOI: 10.1093/HMG/DDV443
Abstract: Sex-specific genetic effects have been proposed to be an important source of variation for human complex traits. Here we use two distinct genome-wide methods to estimate the autosomal genetic correlation (rg) between men and women for human height and body mass index (BMI), using in idual-level (n = ∼44 000) and summary-level (n = ∼133 000) data from genome-wide association studies. Results are consistent and show that the between-sex genetic correlation is not significantly different from unity for both traits. In contrast, we find evidence of genetic heterogeneity between sexes for waist-hip ratio (rg = ∼0.7) and between populations for BMI (rg = ∼0.9 between Europe and the USA) but not for height. The lack of evidence for substantial genetic heterogeneity for body size is consistent with empirical findings across traits and species.
Publisher: Cold Spring Harbor Laboratory
Date: 06-12-2019
DOI: 10.1101/860767
Abstract: 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 robust evidence that 25OHD concentration had causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes had (direct or indirect) causal effects on 25OHD concentration, clarifying the relationship between 25OHD status and health.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-01-2015
Publisher: Elsevier BV
Date: 11-2013
Publisher: Cambridge University Press (CUP)
Date: 02-2012
DOI: 10.1375/TWIN.15.1.87
Abstract: Although it is well established that experience seeking behavior (ES) is positively related to cognitive functioning, the mechanisms underlying this association are not clearly understood. In a large s le of adult twins and siblings (N = 864, age range 23–75), we studied the causes of covariation between ES and general cognitive ability and we studied whether ES moderates the genetic and environmental causes of variation in general cognitive ability. Results demonstrate a phenotypic correlation of .17 (p .001) between general cognitive ability and ES, with a common genetic and common environmental background. Moreover, the extent to which genetic and environmental factors are shared between general cognitive ability and ES is increased in in iduals with either lower or higher levels of ES. In addition, the extent to which genetic and environmental factors influence in idual differences in general cognitive ability in adults partly depended on ES. Standardized influences of additive genetic factors on general cognitive ability ranged from 13% to 99%, with lower estimates in higher levels of ES, while standardized estimates of environmental factors ranged from almost 1% to 87%, with higher estimates in higher levels of ES. Hence, ES and cognitive ability are not only associated through common genetic and environmental factors, but also via moderating effects of genetic and environmental influences on cognitive ability by ES. These findings have implications for future studies on the association between ES and general cognitive ability, and for future research on the genetics of cognitive ability.
Publisher: Annual Reviews
Date: 23-11-2013
DOI: 10.1146/ANNUREV-GENET-111212-133258
Abstract: Understanding genetic variation of complex traits in human populations has moved from the quantification of the resemblance between close relatives to the dissection of genetic variation into the contributions of in idual genomic loci. However, major questions remain unanswered: How much phenotypic variation is genetic how much of the genetic variation is additive and can be explained by fitting all genetic variants simultaneously in one model, and what is the joint distribution of effect size and allele frequency at causal variants? We review and compare three whole-genome analysis methods that use mixed linear models (MLMs) to estimate genetic variation. In all methods, genetic variation is estimated from the relationship between close or distant relatives on the basis of pedigree information and/or single nucleotide polymorphisms (SNPs). We discuss theory, estimation procedures, bias, and precision of each method and review recent advances in the dissection of genetic variation of complex traits in human populations. By using genome-wide data, it is now established that SNPs in total account for far more of the genetic variation than the statistically highly significant SNPs that have been detected in genome-wide association studies. All SNPs together, however, do not account for all of the genetic variance estimated by pedigree-based methods. We explain possible reasons for this remaining “missing heritability.”
Publisher: Springer Science and Business Media LLC
Date: 14-09-2015
DOI: 10.1038/NG.3401
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Springer Science and Business Media LLC
Date: 07-09-2010
DOI: 10.1038/MP.2010.32
Publisher: Elsevier BV
Date: 03-2015
Publisher: Springer Science and Business Media LLC
Date: 29-05-2012
DOI: 10.1038/TP.2012.49
Publisher: Springer Science and Business Media LLC
Date: 17-04-2012
DOI: 10.1038/TP.2012.27
Publisher: Springer Science and Business Media LLC
Date: 14-06-2011
DOI: 10.1038/MP.2011.68
Publisher: Springer Science and Business Media LLC
Date: 16-02-2010
DOI: 10.1038/MP.2010.12
No related grants have been discovered for Anna Vinkhuyzen.