Abdel Abdellaoui
@dr_appie
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Complex Trait Genetics | Population Genetics | Evolutionary Genetics | @AmsterdamUMC | @UvA_Amsterdam
Amsterdam, The Netherlands
Joined July 2015
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Has it been 15 years already? Times flies when you have GWAS 🧬🎂
Check out our new review paper in
@AJHGNews
on the impressive range of GWAS discoveries with remarkable impact on multiple fields.
Thank you
@LoicYengo
, Karin Verweij, and Peter Visscher:
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"We have incorporated all the reviewers' comments, which we believe has substantially improved our work"
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Africa, if its borders were defined by ethnicity and language
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I tried to summarize psychiatric genetics in a figure 🧬🧠
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Academia: train people to get really good at doing research, then have them spend all their time applying for money so they can hire people that they can train to get really good at research so they can also spend all their time applying for money so they can hire etc
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Development of the human brain from 0 to 100 years old 🧠
Based on >120k brain scans from >100k people:
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Genetic effects shared between major psychiatric disorders and a range of behavioral outcomes.
Source:
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Men are less likely than women to pass on genes associated with ADHD, depression, schizophrenia, neuroticism, or autism, while being more likely to pass on genes associated with extraversion, education, or height 🧬
For more sex differences see figure or:
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We tend to reward people with certain genetic propensities with better environments (higher SES 💰). This results in gene-environment correlations that make society more unequal and further complicate studying human genetics.
Out now in
@NatureGenet
:
🧵👇🏽
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I've been developing & teaching this GWAS course since 2009, but will not be teaching it anymore. Some of the material survived since 2009, some of it only appeared recently. Feel free to use anything, this link contains slides, literature, and practicals:
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Check out our new
@NatureHumBehav
article, where we review the history and current state of behavioural genetics and explain how we can further our understanding of the complex relationship between DNA & human behaviour 🧬🤸🏽♂️🧠
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The largest investigation to date on not having had sex late in life:
Our study of >400 thousand individuals links sexlessness to higher education, lower substance use, personality, mental health, physical traits, regional characteristics, and genetics.
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Elon Musk should buy 23andMe and release all GWAS summary statistics
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Genes associated with whether you ever tried cannabis are associated with higher IQ and higher education. Genes associated with cannabis addiction are associated with lower IQ and lower education.
More on genetics of cannabis use in our new review: 🧬🥦
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A dozen major psychiatric conditions interwoven by shared genetic effects 🧬🧠
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Unraveling the genetic architecture of complex traits with genome-wide association studies
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The field of human genetics is evolving at a rapid pace. Much of this progress is driven by our recent ability to link common DNA variants to complex traits with genome-wide association studies (GWASs) 🧬
For both newcomers and seasoned geneticists, good review papers can be
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Industry scientists seem to be more satisfied than those in academia 🧑🏽🔬💰
Academia must step its game up
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Genes associated with ADHD or depression are passed onto more offspring by females than by males. Genes associated with higher extraversion, lower neuroticism, or lower autism risk are passed down more often by males. More sex differences below 👇🏽
From:
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Genes that increase the chances of getting addicted to alcohol increase the risk of feeling lonely. Genes that increase the risk for autism increase IQ. Genes that increase the risk for anorexia increase the chances of getting a higher education 🧬🧠
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According to the biggest human family tree to date, computed from DNA from ~3,600 modern and ~3,600 ancient individuals, early humans originated in Sudan ~2 million years ago 🧬💀
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"If everyone smoked 20 cigarettes a day, then case-control & cohort studies would lead us to conclude that lung cancer is a genetic disease"
From this interesting piece on "sick individuals and sick populations":
How would mental health fit into this?
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"We're the least genetically diverse great ape; 2 groups of chimps from Congo are more genetically different from each other than 2 groups of humans plucked from Berlin & Beijing. Most of our diversity is cultural."
Quote:
Figure:
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Our study on the geographic distribution of human DNA in Great Britain is out in
@NatureHumBehav
.
You can download a general summary and FAQ document here:
The article is here:
And a thread explaining the main findings below 👇🏾
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Many small neuroimaging studies have probably reported false positive findings.
Especially for traits related to cognition & mental health, thousands of subjects are required 🧠
New paper from our talented PhD student Shu Liu in
@NatureHumBehav
:
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Genetic effects that influence where you live can induce gene-environment correlations that confound GWASs. We show that controlling for geography reduces heritability for SES and reduces genetic correlations with SES for many traits.
Our new preprint:
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The heritability of educational attainment for women was close to zero around 1900, in line with the scarcity of opportunities women had to cultivate their talents through education. It increased to ~60% near the end of the century.
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I have a joke about gene-environment interactions, but you won't be able to replicate it
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Between all these behavioural traits, the highest genetic correlation (i.e., most genetic effects shared) is between educational attainment and income 🎓🧬💰
Source:
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This detailed model of a human cell makes me suspect that maybe nature is not really a puzzle meant to be solved, but rather a party to be celebrated
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Funny story: my parents didn't get to finish primary school, I have a PhD, and study the heritability of educational attainment 🤔🤷🏽♂️
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Males are more likely to be left-handed than females, and the number of left-handed people seems to increase over time 🤔 Why?
Data is from
@uk_biobank
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A century ago, height helped to reconcile Mendel’s laws with the inheritance of complex traits. Now,
@LoicYengo
et al made it the first trait to have all its common genetic effects captured, which predict better than the parental average. This is major.
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I have an idea for a dating app. Non-Africans carry 1-2% Neanderthal DNA, but collectively they carry 40% of the Neanderthal genome. The app matches people with non-overlapping Neanderthal DNA. If this gets popular enough, we could recreate 40% Neanderthal - 60% human persons! 🐵
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I dedicate this Manhattan plot of a GWAS on testicle size to all the brave Ukrainian soldiers and citizens that are putting up a fight 🇺🇦
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What kind of genetic propensities are associated with the quality of your life?
See Figure below for estimated genetic correlations (= measure for shared genetic influences) between 55 heritable traits and subjective wellbeing.
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Out now in
@BehaviorGenetic
: genes associated with higher education are selected against, i.e., passed onto fewer offspring.
The direction of this selection pressure is reversed in older mothers, i.e., first child at > ~22 years old.
@davidhughjones
🧬🎓
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The new schizophrenia GWAS is finally out: 69,369 cases, 236,642 controls, and 270 hits.
Preprint:
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Many psychiatric disorders and substance use outcomes share genetic effects. Controlling for genes associated with socio-economic outcomes changes the genetic relationships between these mental health outcomes. Our paper just out in
@NatureHumBehav
🧬💸🧠
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The heritability of a trait is not informative for explaining group differences
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All behavioural traits are heritable. Thanks to large-scale GWAS studies, we now know that this is due to many genes with very small effects. How much larger do GWASs need to get before we capture the total heritability with measured DNA?
Figure from:
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Why aren't we collecting more DNA from the most diverse continent 🧬
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Exactly 1 decade ago today, this little guy joined us using half my genome 🥳
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Which paper(s) have taught you a lot about genetics? 📃🧬
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Winner of the Fulker award (article of the year) from
@BehaviorGenetic
:
One of the findings: women pass on more genes associated with ADHD, depression, schizophrenia, or autism, and men more genes associated with extraversion, education, or height 🧬
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Modern genetics research reveals that part of the answer to the nature/nurture debate lies in the way we organize our society. Would it be possible to find answers to how we should organize our society in the nature/nurture question?
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Sometimes having a higher genetic risk for a psychiatric disorder can also be associated with positive outcomes 🧬🧠
The figure below shows shared genetic effects between psychiatric disorders and a range of behavioral traits (source: )
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What does it mean when genes are associated with intelligence? Much of genetic influences underlying IQ aren't unique to IQ. Here is the estimated overlap between genes associated with IQ (based on ) and a bunch of other traits (rg = genetic correlation).
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The genetic correlation between IQ and subjective wellbeing is zero
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I gave a short tutorial on how to make polygenic scores:
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New
@NatureHumBehav
paper on evolutionary selection pressures on 870 complex traits 🧬⌛️
They conclude that pigmentation, body measurements, and nutrition-related traits showed the most continuous and strong selection pressures throughout human history.
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The journey of the human brain, from birth to 100 years old 🧠
Based on over 120k brain scans from more than 100k individuals:
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World map showing where GWAS participants come from 🤔
Source:
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Genetic effects associated with education, cognition, ADHD, and smoking have stronger associations with brain structure, while genes for other psychiatric disorders show stronger associations with brain function (N🧬&🧠 = 37k).
Check out our new preprint:
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While the polygenic score for height has been decreasing in Great Britain throughout the last century, actual height has consistently increased.
Environment wins!
(data = ~450k
@uk_biobank
participants)
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Here are ~450 thousand
@uk_biobank
participants moving from their birthplace to their current address and back.
For more on migration in Great Britain, see:
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Genes associated with sexuality & reproduction also impact a range of other traits. These outcomes are particularly interesting for genetics because they show a snapshot of natural selection 🧬
Figure from
More on natural selection
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Genes associated with physical appearance diverged faster than other genes. Our visual & tribal propensities may have been the selection pressure causing people to socially cluster based on appearance, making groups of people look more different over time than they actually are.
The geographic distribution of the genetic variant that codes for blue/brown eye colour. If you inherit two G alleles, the chance of blue eyes is ~99%.
It has clearly been under some type of selection for it to be so common in some and so absent in other populations.
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Associations between genes and complex behavioral outcomes reflect a composite of genetic effects on lower-level phenotypes and environmental effects that are correlated with those genetic effects.
Figure comes from:
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I did a GWAS on musical ability and the Manhattan plot came out partying
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The income GWAS got many twitter reactions, almost all negative. The educational attainment GWAS got generally positive reactions.
Income:
EA:
Their genetic correlation is >.9. Why the opposite reactions to almost the same study?
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"Almost everything is heritable"
A short overview of the history, current state, and future of psychiatric genetics 🧬🧠
English:
Original in Dutch:
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I see lots of angry tweeting about Greg Clark's new paper. I don't know how right or how wrong he is, but I do know that he shared all his data! 👏👏👏
So, less tweeting and more sciencing you science kardashians, get to work
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"biological" and "social construct" are not mutually exclusive
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The next game is: extract the causal SNPs from these GWAS summary statistics
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I was scheduled to give the opening keynote lecture at this year's
@ISIRonline
conference in Vienna, but when I saw in the program that
@KirkegaardEmil
would be speaking, I had to cancel. There is no way I will be on the same speaker list as that careless racist lunatic. (1/4)
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Genetic correlations between covid-19 outcomes and cognition, personality, behavior, and physical & mental health 🧬😷
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Genetic correlations between 26 behavioral traits and 26 physical traits 🧬
High quality pdf:
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My favourite genetics project so far is watching this little guy grow up 🧬❤
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Genes survive natural selection pressures by being passed on to offspring.
Below is a measure of natural selection in modern humans of European descent, namely the genetic correlation with nr of offspring based on European GWAS results.
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New GWAS on height is the biggest genetics study to date with 5.4 million individuals 😯
The top ~12k genetic variants explain ~40% of individual differences in Europeans, and 10-20% in other ancestries.
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Among the major psychiatric disorders, schizophrenia and bipolar disorder share most genetic effects (genetic correlation = ~0.7) 🧬🎭
They also have a very similar genetic correlation profile with other traits:
A dozen major psychiatric conditions interwoven by shared genetic effects 🧬🧠
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The International Statistical Genetics Workshop, annually held in Boulder, has its video lectures and practicals organized on a user-friendly website accessible to the global community, which will be further expanded as the field evolves 🧬📏
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Reality probably looks nothing like the model our brain makes for us to observe
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Assortative mating is prevalent across species, often with respect to body size and color. In humans, partners resemble each other most for social traits 🥰
(data for the figure was taken from this meta-analysis by
@GeneWilderType
&
@matthewckeller
: )
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Here is a world map of child malnutrition and infection for all the people posting similar maps of cognitive outcomes claiming genetic differences as the cause
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Grant reviewer: what question do you want to answer with your research?
Me:
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The heritability of IQ varies between socio-economic groups: in the US, genes explain fewer individual differences in IQ in economically disadvantaged families than in richer families, likely because the former lack means to facilitate the expression of genetic potential.
The heritability of educational attainment for women was close to zero around 1900, in line with the scarcity of opportunities women had to cultivate their talents through education. It increased to ~60% near the end of the century.
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Peter Visscher: "In my opinion, genomics should be fully embedded into the social sciences. If a substantial portion of differences between people in important life outcomes is due to DNA, why not utilise it to design better experiments and inform policy?"
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The drop in whole-genome sequencing costs on a logarithmic and a linear scale
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Relationships between functional brain measures and polygenic scores for mental health, cognition, and educational attainment.
From:
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