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Ian W. Craig

Bio: Ian W. Craig is an academic researcher from King's College London. The author has contributed to research in topics: Single-nucleotide polymorphism & Genome-wide association study. The author has an hindex of 69, co-authored 217 publications receiving 23650 citations. Previous affiliations of Ian W. Craig include University of London & University of Cambridge.


Papers
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Journal ArticleDOI
02 Aug 2002-Science
TL;DR: In this paper, a large sample of male children from birth to adulthood was studied to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not.
Abstract: We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.

4,151 citations

Journal ArticleDOI
S. Hong Lee1, Stephan Ripke2, Stephan Ripke3, Benjamin M. Neale3  +402 moreInstitutions (124)
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

2,058 citations

Journal ArticleDOI
TL;DR: These findings provide the strongest evidence to date suggesting that the MAOA gene influences vulnerability to environmental stress, and that this biological process can be initiated early in life.
Abstract: Previous research on adults has shown that a functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene moderates the impact of childhood maltreatment on risk for developing antisocial behavior. Thus far, attempts to replicate this finding have been mixed. The current study (i) presents new data investigating this finding in a sample of 975 seven-year-old boys, and (ii) evaluates the extant data by conducting a meta-analysis of published findings. We replicated the original finding by showing that the MAOA polymorphism moderates the development of psychopathology after exposure to physical abuse, we extended the finding to childhood closer in time to the maltreatment experience, and we ruled-out the possibility of a spurious finding by accounting for passive and evocative gene-environment correlation. Moreover, meta-analysis demonstrated that across studies, the association between maltreatment and mental health problems is significantly stronger in the group of males with the genotype conferring low vs high MAOA activity. These findings provide the strongest evidence to date suggesting that the MAOA gene influences vulnerability to environmental stress, and that this biological process can be initiated early in life.

1,083 citations

Journal ArticleDOI
Stephan Ripke1, Naomi R. Wray2, Cathryn M. Lewis3, Steven P. Hamilton4, Myrna M. Weissman5, Gerome Breen3, Enda M. Byrne2, Douglas Blackwood6, Dorret I. Boomsma7, Sven Cichon8, Andrew C. Heath9, Florian Holsboer, Susanne Lucae4, Pamela A. F. Madden9, Nicholas G. Martin2, Peter McGuffin3, Pierandrea Muglia8, Markus M. Noethen10, Brenda P Penninx7, Michele L. Pergadia9, James B. Potash11, Marcella Rietschel10, Danyu Lin12, Bertram Müller-Myhsok8, Jianxin Shi13, Stacy Steinberg8, Hans J. Grabe, Paul Lichtenstein14, Patrik K. E. Magnusson14, Roy H. Perlis7, Martin Preisig15, Jordan W. Smoller16, Kari Stefansson, Rudolf Uher3, Zoltán Kutalik17, Katherine E. Tansey3, Alexander Teumer, Alexander Viktorin14, Michael R. Barnes11, Thomas Bettecken18, Elisabeth B. Binder19, René Breuer10, Victor M. Castro20, Susanne Churchill13, William Coryell11, Nicholas John Craddock, Ian W. Craig3, Darina Czamara6, Eco J. C. de Geus7, Franziska Degenhardt8, Anne Farmer3, Maurizio Fava16, Josef Frank10, Vivian S. Gainer, Patience J. Gallagher16, Scott D. Gordon2, Sergey Goryachev, Magdalena Gross8, Michel Guipponi21, Anjali K. Henders2, Stefan Herms8, Ian B. Hickie22, Susanne Hoefels8, Witte J.G. Hoogendijk3, Jouke-Jan Hottenga7, Dan V. Iosifescu16, Marcus Ising9, Ian Jones2, Lisa Jones22, Tzeng Jung-Ying15, James A. Knowles18, Isaac S. Kohane16, Martin A. Kohli2, Ania Korszun9, Mikael Landén5, William Lawson19, Glyn Lewis23, Donald J. MacIntyre6, Wolfgang Maier8, Manuel Mattheisen8, Patrick J. McGrath5, Andrew M. McIntosh6, Alan W. McLean6, Christel M. Middeldorp7, Lefkos T. Middleton23, G. M. Montgomery2, Shawn N. Murphy16, Matthias Nauck, Willem A. Nolen, Dale R. Nyholt2, Michael Conlon O'Donovan24, Hogni Oskarsson, Nancy L. Pedersen14, William A. Scheftner20, Andrea Schulz, Thomas G Schulze16, Stanley I. Shyn9, Engilbert Sigurdsson, Susan L. Slager25, Johannes H. Smit7, Hreinn Stefansson17, Michael Steffens8, Thorgeir E. Thorgeirsson, Federica Tozzi, Jens Treutlein10, Manfred Uhr, Edwin J. C. G. van den Oord26, Gerard van Grootheest7, Henry Völzke14, Jeffrey B. Weilburg16, Gonneke Willemsen7, Frans G. Zitman27, Benjamin M. Neale, Mark J. Daly1, Douglas F. Levinson28, Patrick F. Sullivan12 
TL;DR: This article conducted a genome-wide association studies (GWAS) mega-analysis for major depressive disorder (MDD) using more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18,759 independent and unrelated subjects of recent European ancestry.
Abstract: Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

989 citations


Cited by
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Journal Article
TL;DR: For the next few weeks the course is going to be exploring a field that’s actually older than classical population genetics, although the approach it’ll be taking to it involves the use of population genetic machinery.
Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

9,847 citations

Journal ArticleDOI
18 Jul 2003-Science
TL;DR: Evidence of a gene-by-environment interaction is provided, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
Abstract: In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

7,210 citations

Journal ArticleDOI
02 Aug 2002-Science
TL;DR: In this paper, a large sample of male children from birth to adulthood was studied to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not.
Abstract: We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.

4,151 citations

Journal ArticleDOI
TL;DR: It is found that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size, and the LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control.
Abstract: Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.

3,708 citations

Journal ArticleDOI
Markus Schuelke1
TL;DR: A poor man's approach to genotyping for research and high-throughput diagnostics and how it can be applied to medicine and science.
Abstract: A poor man's approach to genotyping for research and high-throughput diagnostics.

3,421 citations