Ben’s research and training focuses heavily on the development and application of statistical methodology with a focus on methods specifically for genetic analysis. Ben has a strong track record of conducting analyses for genetic data with a heavy focus on psychiatric illness, particularly ADHD and Autism, but also Tourette’s Obsessive Compulsive Disorder, Schizophrenia and Eating Disorders.
Ben in collaboration with Drs. Manuel Ferreira, Sarah Medland, and Danielle Posthuma, edited a book entitled “Statistical Genetics: Gene-mapping through Linkage and Association,” that provides a practical hands-on guide for the analysis of current genetic datasets as well providing a background in both the statistical and genetic elements necessary to conduct such analyses. Beyond this, Ben substantively aided in the development of PLINK, which is one of the most highly used packages for genetic association analysis and is currently collaborating closely with Dr. Shaun Purcell on the development of a new analytic package for sequence data title PLINK/SEQ. Currently, Ben is lead analyst for one of the largest exome sequencing projects on a psychiatric disorder, the NIMH ARRA Autism project, and am collaborating with Dr. Patrick Sullivan on clozapine-induced agranulocytosis, a devastating side effect of what is regarded as one of the more effective anti-psychotic medicines. Ben also serves as the chair of the analysis for the ADHD PGC subgroup and is a member of the Autism group, Analysis group, and the Cross-Disorder Group in the PGC.
Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection.
Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.
Am J Med Genet B Neuropsychiatr Genet. 2017;:ePub - PMID: 28719003
Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.
Genes Brain Behav. 2017;:ePub - PMID: 28719030
Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders.
Nat Neurosci. 2017;:ePub - PMID: 28671696
Quantifying the genetic correlation between multiple cancer types.
Cancer Epidemiol Biomarkers Prev. 2017;:ePub - PMID: 28637796
Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.
Neuron. 2017;94(6):1101-1111.e7 - PMID: 28641109
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Neuron. 2017;94(3):486-499.e9 - PMID: 28472652
Phenome-wide heritability analysis of the UK Biobank.
PLoS Genet. 2017;13(4):e1006711 - PMID: 28388634
Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations.
Am J Hum Genet. 2017;:ePub - PMID: 28366442
A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.
Functional Architectures of Local and Distal Regulation of Gene Expression in Multiple Human Tissues.
Am J Hum Genet. 2017;:ePub - PMID: 28343628
Large-Scale trans-eQTLs Affect Hundreds of Transcripts and Mediate Patterns of Transcriptional Co-regulation.
Am J Hum Genet. 2017;:ePub - PMID: 28285767
The Weighting is the Hardest Part: On the Behavior of the Likelihood Ratio Test and the Score Test Under a Data-Driven Weighting Scheme in Sequenced Samples.
Twin Res Hum Genet. 2017;:1-11 - PMID: 28238293
Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples.
A framework for the detection of de novo mutations in family-based sequencing data.
Eur J Hum Genet. 2016;:ePub - PMID: 27876817
No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study.
Ultra-rare disruptive and damaging mutations influence educational attainment in the general population.
LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis.
Bioinformatics. 2016;:ePub - PMID: 27663502
Erratum: A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.
Nat Commun. 2016;7:12869 - PMID: 27619887
Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
Nat Genet. 2016;48(10):1296 - PMID: 27681292
Analysis of protein-coding genetic variation in 60,706 humans.
Nature. 2016;536(7616):285-91 - PMID: 27535533
A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.
Nat Commun. 2016;7:12342 - PMID: 27503255
A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.
J Am Acad Child Adolesc Psychiatry. 2016;55(10):896-905.e6 - PMID: 27663945
Association of Exome Sequences with Cardiovascular Traits among African Americans in the Jackson Heart Study.
Circ Cardiovasc Genet. 2016;:ePub - PMID: 27422940
The genetic architecture of type 2 diabetes.
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
Discovery of rare variants for complex phenotypes.
Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.
JAMA Psychiatry. 2016;:ePub - PMID: 27167565
A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.
Am J Hum Genet. 2016;:ePub - PMID: 27087321
The statistical properties of gene-set analysis.
Nat Rev Genet. 2016;:ePub - PMID: 27070863
Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population.
Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.
Nat Neurosci. 2016;:ePub - PMID: 26854805
Genetic effect of chemotherapy exposure in children of testicular cancer survivors.
Clin Cancer Res. 2015;:ePub - PMID: 26631610
Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis.
Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores.
Am J Hum Genet. 2015;97(4):576-92 - PMID: 26430803
An atlas of genetic correlations across human diseases and traits.
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
Partitioning heritability by functional annotation using genome-wide association summary statistics.
Genome-wide autozygosity is associated with lower general cognitive ability.
Genetic research in autism spectrum disorders.
Curr Opin Pediatr. 2015;:ePub - PMID: 26371945
Phenotypic extremes in rare variant study designs.
Eur J Hum Genet. 2015;:ePub - PMID: 26350511
New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis.
Int J Epidemiol. 2015;:ePub - PMID: 26286434
Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.
Transl Psychiatry. 2015;5:e607 - PMID: 26196440
The Genetics of Neuropsychiatric Diseases: Looking In and Beyond the Exome.
Annu Rev Neurosci. 2015;:ePub - PMID: 25840007
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.
Efficient Bayesian mixed-model analysis increases association power in large cohorts.
Exome Sequencing in Suspected Monogenic Dyslipidemias.
Circ Cardiovasc Genet. 2015;:ePub - PMID: 25632026
No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins.
PLoS Genet. 2015;11(1):e1004852 - PMID: 25621974
Genetic analysis of schizophrenia and bipolar disorder reveals polygenicity but also suggests new directions for molecular interrogation.
Curr Opin Neurobiol. 2014;30C:131-138 - PMID: 25544106
Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence.
N Engl J Med. 2014;:ePub - PMID: 25426838
Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases.
Synaptic, transcriptional and chromatin genes disrupted in autism.
Autism spectrum disorder severity reflects the average contribution of de novo and familial influences.
Proc Natl Acad Sci U S A. 2014;:ePub - PMID: 25288738
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
Nat Commun. 2014;5:4757 - PMID: 25187353
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
Am J Psychiatry. 2014;:ePub - PMID: 25158072
Attention-deficit/hyperactivity disorder polygenic risk scores predict attention problems in a population-based sample of children.
J Am Acad Child Adolesc Psychiatry. 2014;53(10):1123-1129.e6 - PMID: 25245356
A framework for the interpretation of de novo mutation in human disease.
Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
J Am Acad Child Adolesc Psychiatry. 2014;53(8):910-9 - PMID: 25062598
Whole-genome analyses of whole-brain data: working within an expanded search space.
Nat Neurosci. 2014;17(6):791-800 - PMID: 24866045
Rare deleterious mutations of the gene EFR3A in autism spectrum disorders.
Copy number variation in schizophrenia in Sweden.
Mol Psychiatry. 2014;:ePub - PMID: 24776740
Statistical Properties of Single-Marker Tests for Rare Variants.
Twin Res Hum Genet. 2014;:1-8 - PMID: 24739319
Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.
An excess of risk-increasing low-frequency variants can be a signal of polygenic inheritance in complex diseases.
Searching for missing heritability: Designing rare variant association studies.
Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.
Nature. 2013;506(7486):97-101 - PMID: 24390345
Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.
Common variants associated with plasma triglycerides and risk for coronary artery disease.
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
High loading of polygenic risk for ADHD in children with comorbid aggression.
Genome-wide meta-analysis identifies new susceptibility loci for migraine.
Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants.
Am J Med Genet B Neuropsychiatr Genet. 2013;162B(5):419-30 - PMID: 23728934
Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls.
Patterns and rates of exonic de novo mutations in autism spectrum disorders.