Benjamin Neale

Last updated
Benjamin Neale
Education University of Chicago
Virginia Commonwealth University (B.Sc., 2006) [1]
King's College London (Ph.D., 2009) [2]
Known for Psychiatric genetics
Awards Leena Peltonen Prize for Excellence in Human Genetics (2016)
Scientific career
Fields Human genetics
Statistical genetics
Institutions Broad Institute
Harvard Medical School
Massachusetts General Hospital
Website www.nealelab.is

Benjamin Michael Neale is a statistical geneticist with a specialty in psychiatric genetics. He is an institute member at the Broad Institute as well as an associate professor at both Harvard Medical School and the Analytic and Translational Genetics Unit at Massachusetts General Hospital. [3] Neale specializes in genome-wide association studies (GWAS). [3] He was responsible for the data analysis of the first GWAS on attention-deficit/hyperactivity-disorder, and he developed new analysis software such as PLINK, [4] which allows for whole-genome data to be analyzed for specific gene markers. Related to his work on GWAS, Neale is the lead of the ADHD psychiatric genetics and also a member of the Psychiatric GWAS Consortium analysis committee.[ citation needed ][ not verified in body ]

Contents

Education

Neale's academic background includes a Genetics Bachelor's of Science degree from the University of Chicago and a Ph.D. in human genetics from King’s College. His postdoctoral project was done in the laboratory of Mark Daly at Massachusetts General Hospital. [5] Neale was recently awarded the 2020 Early-Career Award by the American Society of Human Genetics for his emphasis on using statistical methodology in his research analyses. [6]

Research

Neale has published work on autism and genetic contributions to disease. In 2010, Neale wrote about the function of the hepatic lipase gene, LIPC. [7] The experiment found an association between advanced age-related macular degeneration (AMD), which is the main culprit of late onset blindness, and genetic variants in LIPC of the high-density lipoprotein cholesterol (HDL) pathway. The strongest association was found for rs10468017, which correlated with a protective, HDL-increasing effect of the T allele involved in AMD. Weaker associations were found for other LIPC loci ABCA1 and FADS1-3. The impact of this research lies in its examination of previously unthought-of pathways involved in the development of AMD.[ citation needed ]

In 2014, Neale contributed to a paper on the design of scientific disease studies focusing on uncommon genetic variants. The article included the operationalization of variables, advice on sample size, discussion of alleles and their frequencies, and information on noncoding and regions of the genome. [8]

That same year, he contributed on a paper examining the gene variant that allows for the experience of euphoria when taking d-amphetamine and connecting it to decreased risk for developing schizophrenia and ADHD. [9] In particular, the research found increased expression, or enrichment, of certain alleles associated with increased sensitivity to amphetamine-induced euphoria and decreased sensitivity to developing schizophrenia and ADHD. This work opens new possibilities to use the alleles that demonstrated changes in expression in order to analyze risk for developing neurological disorders that involve dopamine. Dopamine is the chemical in d-amphetamine that is responsible for its euphoric effects, and some disorders such as schizophrenia involve abnormal dopamine levels, though other factors are involved.[ citation needed ]

Neale has also researched influences on behaviors indicative of autism, namely that of de novo and familial factors. [10] The purpose of the study was to analyze IQ scores, assessments of behavior and language, spontaneous loss of function mutations, and familial history of mental illness. The study found a negative association between IQ scores and spontaneous loss of function mutation rates, and a positive association between IQ scores and family history of mental illness. This study suggests family history of mental illness could play a more influential role than previously thought in the phenotypic and genetic manifestations of autism.[ citation needed ]

In 2022, Neale co-published a study which linked potential genetic variants with bipolar disorder, saying "the long-term hope is that the genetic discoveries can form the basis of better understanding of the underlying biological processes that are involved in bipolar disorder". [11] [12]

Awards

In 2016, Neale received the second Leena Peltonen Prize for Excellence in Human Genetics from the Paulo Foundation in Finland. Neale was given the award in recognition of his work in the fields of statistical and psychiatric genetics. [2] This has included research on the genetics of psychiatric disorders such as schizophrenia, major depression, [12] [13] and autism. [14]

Personal life

Neale is openly gay. [15]

Related Research Articles

<span class="mw-page-title-main">Causes of mental disorders</span> Etiology of psychopathology

A mental disorder is an impairment of the mind disrupting normal thinking, feeling, mood, behavior, or social interactions, and accompanied by significant distress or dysfunction. The causes of mental disorders are very complex and vary depending on the particular disorder and the individual. Although the causes of most mental disorders are not fully understood, researchers have identified a variety of biological, psychological, and environmental factors that can contribute to the development or progression of mental disorders. Most mental disorders result in a combination of several different factors rather than just a single factor.

<span class="mw-page-title-main">Pleiotropy</span> Influence of a single gene on multiple phenotypic traits

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function.

<span class="mw-page-title-main">Norepinephrine transporter</span> Protein-coding gene in the species Homo sapiens

The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene.

<span class="mw-page-title-main">Heritability of autism</span> The rate at which autism is inherited

The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. Autism has a strong genetic basis. Although the genetics of autism are complex, autism spectrum disorder (ASD) is explained more by multigene effects than by rare mutations with large effects.

<span class="mw-page-title-main">Monoamine oxidase A</span> Endogenous enzyme

Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. A mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed.

Psychiatric genetics is a subfield of behavioral neurogenetics and behavioral genetics which studies the role of genetics in the development of mental disorders. The basic principle behind psychiatric genetics is that genetic polymorphisms are part of the causation of psychiatric disorders.

Peter McGuffin was a Northern Irish psychiatrist and geneticist from Belfast.

Schizophrenia is a neurodevelopmental disorder with no precise or single cause. Schizophrenia is thought to arise from multiple mechanisms and complex gene–environment interactions with vulnerability factors. Risk factors of schizophrenia have been identified and include genetic factors, environmental factors such as experiences in life and exposures in a person's environment, and also the function of a person's brain at it develops. The interactions of these risk factors are intricate, as numerous and diverse medical insults from conception to adulthood can be involved. Many theories have been proposed including the combination of genetic and environmental factors may lead to deficits in the neural circuits that affect sensory input and cognitive functions.

<span class="mw-page-title-main">Genome-wide association study</span> Study of genetic variants in different individuals

In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.

<span class="mw-page-title-main">DISC1</span> Protein-coding gene in the species Homo sapiens

Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research. Although, recent genetic studies of large schizophrenia cohorts have failed to implicate DISC1 as a risk gene at the gene level, the DISC1 interactome gene set was associated with schizophrenia, showing evidence from genome-wide association studies of the role of DISC1 and interacting partners in schizophrenia susceptibility.

In multivariate quantitative genetics, a genetic correlation is the proportion of variance that two traits share due to genetic causes, the correlation between the genetic influences on a trait and the genetic influences on a different trait estimating the degree of pleiotropy or causal overlap. A genetic correlation of 0 implies that the genetic effects on one trait are independent of the other, while a correlation of 1 implies that all of the genetic influences on the two traits are identical. The bivariate genetic correlation can be generalized to inferring genetic latent variable factors across > 2 traits using factor analysis. Genetic correlation models were introduced into behavioral genetics in the 1970s–1980s.

<span class="mw-page-title-main">Neuregulin 3</span> Protein-coding gene in Homo sapiens

Neuregulin 3, also known as NRG3, is a neural-enriched member of the neuregulin protein family which in humans is encoded by the NRG3 gene. The NRGs are a group of signaling proteins part of the superfamily of epidermal growth factor, EGF like polypeptide growth factor. These groups of proteins possess an 'EGF-like domain' that consists of six cysteine residues and three disulfide bridges predicted by the consensus sequence of the cysteine residues.

<span class="mw-page-title-main">Neurogenomics</span> Part of the study of the genome

Neurogenomics is the study of how the genome of an organism influences the development and function of its nervous system. This field intends to unite functional genomics and neurobiology in order to understand the nervous system as a whole from a genomic perspective.

Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates the extent to which genetic and environmental factors influence individual differences, and the development of research designs that can remove the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans, as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research and in human studies, leading to new scientific discoveries.

The Center for Applied Genomics is a research center at the Children's Hospital of Philadelphia that focuses on genomics research and the utilization of basic research findings in the development of new medical treatments.

The missing heritability problem arises from the difference between heritability estimates from genetic data and heritability estimates from twin and family data across many physical and mental traits, including diseases, behaviors, and other phenotypes. This is a problem that has significant implications for medicine, since a person's susceptibility to disease may depend more on the combined effect of all the genes in the background than on the disease genes in the foreground, or the role of genes may have been severely overestimated.

Joseph D. Buxbaum is an American molecular and cellular neuroscientist, autism researcher, and the Director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai. Buxbaum is also, along with Simon Baron-Cohen, the co-editor of the BioMed Central journal Molecular Autism, and is a member of the scientific advisory board of the Autism Science Foundation. Buxbaum is a Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences. He is also the Vice Chair for Research and for Mentoring in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai.

<span class="mw-page-title-main">Complex traits</span>

Complex traits are phenotypes that are controlled by two or more genes and do not follow Mendel's Law of Dominance. They may have a range of expression which is typically continuous. Both environmental and genetic factors often impact the variation in expression. Human height is a continuous trait meaning that there is a wide range of heights. There are an estimated 50 genes that affect the height of a human. Environmental factors, like nutrition, also play a role in a human's height. Other examples of complex traits include: crop yield, plant color, and many diseases including diabetes and Parkinson's disease. One major goal of genetic research today is to better understand the molecular mechanisms through which genetic variants act to influence complex traits. Complex traits are also known as polygenic traits and multigenic traits.

Personality traits are patterns of thoughts, feelings and behaviors that reflect the tendency to respond in certain ways under certain circumstances.

Sagiv Shifman is an Israeli scientist, professor in the field of neurogenetics at the Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem. He holds the Arnold and Bess Zeldich Ungerman chair in Neurobiology.

References

  1. ↑ "The Editors". Statistical Genetics. Retrieved 2018-09-20.
  2. 1 2 "The second Leena Peltonen Prize for Excellence in Human Genetics to Dr. Benjamin Neale". EurekAlert! (Press release). 2016-03-03. Retrieved 2018-09-20.
  3. 1 2 "Benjamin Neale". Broad Institute. 2015-06-29. Retrieved 2018-09-20.
  4. ↑ Purcell, Shaun; Neale, Benjamin; Todd-Brown, Kathe; Thomas, Lori; Ferreira, Manuel A.R.; Bender, David; Maller, Julian; Sklar, Pamela; De Bakker, Paul I.W.; Daly, Mark J.; Sham, Pak C. (2007-09-01). "PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses". The American Journal of Human Genetics. 81 (3): 559–575. doi:10.1086/519795. ISSN   0002-9297. PMC   1950838 . PMID   17701901.
  5. ↑ "Benjamin Neale". Broad Institute. 2015-06-29. Retrieved 2020-11-17.
  6. ↑ Md 20852 (2020-07-13). "ASHG". ASHG. Retrieved 2020-11-17.{{cite web}}: CS1 maint: numeric names: authors list (link)
  7. ↑ Neale, Benjamin (2010). "Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)". Proceedings of the National Academy of Sciences. 107 (16): 7396–7400. Bibcode:2010PNAS..107.7395N. doi: 10.1073/pnas.0912019107 . JSTOR   25665364. PMC   2867697 . PMID   20385826.
  8. ↑ Neale, Benjamin (January 28, 2014). "Searching for missing heritability: Designing rare variant association studies". Proceedings of the National Academy of Sciences. 111 (4): E455-64. Bibcode:2014PNAS..111E.455Z. doi: 10.1073/pnas.1322563111 . JSTOR   23769021. PMC   3910587 . PMID   24443550.
  9. ↑ Neale, Benjamin (April 22, 2014). "Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder". Proceedings of the National Academy of Sciences. 111 (16): 5968–5973. Bibcode:2014PNAS..111.5968H. doi: 10.1073/pnas.1318810111 . JSTOR   23771486. PMC   4000861 . PMID   24711425.
  10. ↑ Neale, Benjamin (October 21, 2014). "Autism spectrum disorder severity reflects the average contributions of de novo and familial influences". Proceedings of the National Academy of Sciences. 111 (42): 15161–15165. Bibcode:2014PNAS..11115161R. doi: 10.1073/pnas.1409204111 . JSTOR   43189895. PMC   4210299 . PMID   25288738.
  11. ↑ Cosgrove, Jonathan A.; Lu, Andrew M. (22 April 2022). "HMS and Broad Institute Researchers Discover First Strong Genetic Link to Bipolar Disorder | News | The Harvard Crimson". www.thecrimson.com. Retrieved 2023-11-21.
  12. 1 2 Makin, Simon (2014-10-16). "Schizophrenia's Genetic Roots". Scientific American Mind. 25 (6): 13. doi:10.1038/scientificamericanmind1114-13 . Retrieved 2018-09-20.
  13. ↑ "Same genes drive several psychiatric conditions, study says". UPI. 2018-06-22. Retrieved 2018-09-20.
  14. ↑ Yong, Ed (2013-10-25). "Genetic Test for Autism Refuted". The Scientist Magazine. Retrieved 2018-09-20.
  15. ↑ Belluck, Pam (2019-08-29). "Many Genes Influence Same-Sex Sexuality, Not a Single 'Gay Gene'". The New York Times. ISSN   0362-4331 . Retrieved 2019-08-29.
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