Alex Strudwick Young @AlexTISYoung Twitter profile

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Alex Strudwick Young

@AlexTISYoung

21 days

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Alex Strudwick Young

@AlexTISYoung

1 year

@jonatanpallesen If the apparent placebo depends mostly on a tendency to regress to a healthy mean, there should be no placebo effect in RCTs of terminal cancer patients, or Alzheimer's disease, or other diseases that follow a predictable deterioration path. Is that true?

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Alex Strudwick Young

@AlexTISYoung

1 year

In PNAS today, Greg Clark documents the inheritance of social status in an impressive dataset on 422,374 people born in England between 1600 to 2022. Clark finds a strong persistence in social status going from close to distant relatives, which fits a model dating back to RA

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Alex Strudwick Young

@AlexTISYoung

3 years

New educational attainment (EA) GWAS out today: . We expand the sample size from ~1 million to ~3 million, making it one of the largest GWAS to date. We identify more loci affecting EA and increase our ability to predict EA from genetic data, and more...🧵

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Alex Strudwick Young

@AlexTISYoung

5 years

Noah is someone I know personally from Oxford. I don't agree with his politics or some of the conclusions of his research, but I know he is an intelligent and open minded truth seeker. If there is no place for heterodox scholars in the academy, that's very worrying.

Claire Lehmann

@clairlemon

6 years

I have just learned that the mob has been successful in getting social scientist Noah Carl fired from his position at Cambridge. The statement from St. Edmund's apologises for the "hurt" caused by his appointment. Read the back-story here

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Alex Strudwick Young

@AlexTISYoung

2 years

Out today in @NatureGenet , our paper showing how to increase power for family-based analyses by imputing missing parental genotypes: . We apply our software () to 9 phenotypes, demonstrating confounding in standard GWAS and more..🧵

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Alex Strudwick Young

@AlexTISYoung

2 years

Impressive work finds 8 genes with a large effect on educational attainment in UKB whole exome data. Mouse knockouts of one of the genes, Kdm5b, show impaired memory. The people who said genomic studies of education would never reveal any meaningful biology were wrong.

Chia-Yen Chen

@ChiayenChen

2 years

New preprint! We studied how rare protein-coding variants impact cognitive function & linked diseases in @uk_biobank . We identified 8 large-effect cog fx genes, dosage-sensitivity for KDM5B, additivity of rare variant and polygenic risk & more (1/12)

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Alex Strudwick Young

@AlexTISYoung

2 years

One can add the throttling of academic freedom as another factor contributing to the exodus to industry. Why accept a lower salary and worse conditions if you can't research what you want or speak freely?

Academia’s lost luster prompts exodus of health researchers to industry

Nature Medicine - A desire for better work conditions and real-world impact are behind the movement, which may hinder academic clinical trials while leading to beneficial collaborations.

www.nature.com

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Alex Strudwick Young

@AlexTISYoung

1 year

The discussion around Greg Clark's paper () on the inheritance of social status has centered on whether models other than a genetic model can explain observed relative correlations. It has been known since the work of Cloninger, Rice, and Reich in the

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Alex Strudwick Young

@AlexTISYoung

2 years

Out today in @ScienceMagazine , our paper on cross-trait assortative mating and why estimates of genetic correlations (i.e. shared genetic effects on phenotypes) are likely inflated. See this thread from the preprint for an overview of the idea and results

Alex Strudwick Young

@AlexTISYoung

3 years

New from Richard Border @andywdahl @flint Noah Zaitlen myself & others. Estimated genetic correlations between traits may be inflated by cross-trait assortative mating (xAM): . So are apparent genetic relationships between traits a statistical artefact? 🧵

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Alex Strudwick Young

@AlexTISYoung

3 years

I wrote an article for Nature Genetics () giving my view on the newly published work measuring heritability using whole-genome data. WGS data will give us a more complete picture of the sources of heritable variation than ever before. 🧵

Jian Yang

@jyang1981

3 years

This study quantifies the overall contributions of both common and rare variants to the phenotypic variation in a complex trait (height or BMI in this case),

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Alex Strudwick Young

@AlexTISYoung

2 years

Comprehensive analysis of dominance (non-additive) effects in UK Biobank () finds negligible non-additive variance from common variants. However, it also finds that variants with large effects or phenotypes whose genetic architecture is dominated by a small

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Alex Strudwick Young

@AlexTISYoung

1 year

My paper is out! . Assortative mating (AM) occurs when parents' phenotypes are correlated. My paper aims to solve problems AM creates for estimation of indirect genetic effects (IGEs) and heritability by developing theory and an estimation method...🧵

Estimation of indirect genetic effects and heritability under assortative mating

Both direct genetic effects (effects of alleles in an individual on that individual) and indirect genetic effects — effects of alleles in an individual (e.g. parents) on another individual (e.g....

www.biorxiv.org

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Alex Strudwick Young

@AlexTISYoung

6 years

Out today in @NatureGenet : our paper on RDR, a novel method for estimating heritability without environment bias (). I wrote an accessible blog post explaining the paper and its implications () #genetics

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Alex Strudwick Young

@AlexTISYoung

3 years

New from Richard Border @andywdahl @flint Noah Zaitlen myself & others. Estimated genetic correlations between traits may be inflated by cross-trait assortative mating (xAM): . So are apparent genetic relationships between traits a statistical artefact? 🧵

Cross-trait assortative mating is widespread and inflates genetic correlation estimates

The observation of genetic correlations between disparate traits has been interpreted as evidence of widespread pleiotropy, altered theories of human genetic architecture, and spurred considerable...

www.biorxiv.org

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Alex Strudwick Young

@AlexTISYoung

1 year

I'm a reviewing editor at eLife, and I'm opposed to removing @mbeisen for his social media posts. It is bad for scientific culture when the expression of unpopular opinions is policed with extreme strictness. This is true whether those opinions are thought of as 'right-wing' or

Nancy Kanwisher @[email protected]

@Nancy_Kanwisher

1 year

If you are a tenured professor in the life/neuro sciences who values open exchange of ideas in academia, please sign our new petition telling HHMI and eLife not to censure Michael Eisen for tweeting about the Middle East. @eLife and @HHMINews

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Alex Strudwick Young

@AlexTISYoung

1 year

Further thoughts on Greg Clark's recent work in PNAS. The paper has two major contributions: 1) Construction of a large genealogical database on 422,374 people born in England between 1600 and 2022 along with measures of social status — occupational status, higher education

Alex Strudwick Young

@AlexTISYoung

1 year

In PNAS today, Greg Clark documents the inheritance of social status in an impressive dataset on 422,374 people born in England between 1600 to 2022. Clark finds a strong persistence in social status going from close to distant relatives, which fits a model dating back to RA

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Alex Strudwick Young

@AlexTISYoung

9 months

@mattyglesias This is known as the problem of missing heritability. What we can account for by GWAS is not the same as the total heritability, but some argue that twin estimates are still too high. I wrote an accessible article discussing these issues:

Solving the missing heritability problem

journals.plos.org

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Alex Strudwick Young

@AlexTISYoung

10 months

@miniapeur "Young man, in mathematics you don't understand things. You just get used to them." von Neumann

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Alex Strudwick Young

@AlexTISYoung

1 year

In @TrendsGenetics today, @hilsomartin and I deliver a spotlight () on the recent exome-wide association study of education and cognitive ability. Our concluding paragraph states: The study by Chen et al. provides a compelling rebuke to those who have

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Alex Strudwick Young

@AlexTISYoung

6 years

New blog on 'missing heritability' and the preprint on estimating heritability from whole genome sequence (). Complements my appearance on the @insight_podcast with @razibkhan (). Missing heritability not yet solved. #genetics

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Alex Strudwick Young

@AlexTISYoung

1 year

John Carlisle, an editor of Anaesthesia, found that 25% of randomized controlled trials (RCTs) had data that was impossible to trust when examined at the individual participant level, but only 1% had such obvious flaws in the summary data reported in the journal article. People

Richard Van Noorden

@Richvn

1 year

Some researchers say that at least a quarter of randomized clinical trials in some fields are untrustworthy (perhaps fake?!), but still cited in reviews that guide medical practice. How big is this problem & what's the evidence? Here's my look in @Nature

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Alex Strudwick Young

@AlexTISYoung

7 years

My manuscript on estimating heritability without environmental bias ( ) and Augie Kong's manuscript on the nature of nurture ( ) out now on @biorxivpreprint . Heritability and genetic association may not be as they seem. #Genetics

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Alex Strudwick Young

@AlexTISYoung

5 years

Our review article on 'Deconstructing the sources of genotype-phenotype association in humans' out today in @sciencemagazine (). We lay out the contributions to genotype-phenotype associations, and the value of family data for separating them. @molly_przew

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Alex Strudwick Young

@AlexTISYoung

7 months

To accompany @carl_veller and @Graham_Coop 's recent article in @PLOSBiology , I wrote an accessible primer on family-based genome-wide association studies: Genome-wide association studies (GWASs) can be affected by confounding. Family-based GWAS uses random, within-family genetic

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Alex Strudwick Young

@AlexTISYoung

2 years

3.4 million person GWAS of smoking and alcohol use: . Polygenic predictors can now explain 10% of the variation in smoking initiation. An example of the utility of behavioural GWAS for biomedicine: genes influence smoking behaviour and therefore health

Genetic diversity fuels gene discovery for tobacco and alcohol use

Nature - A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

www.nature.com

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Alex Strudwick Young

@AlexTISYoung

5 years

My opinion piece on the missing heritability problem, what we know about it, and the challenges any solution to it would have to overcome. #genetics #Genomics

Solving the missing heritability problem

journals.plos.org

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Alex Strudwick Young

@AlexTISYoung

28 days

Large-scale genomic analysis of metabolic syndrome highlights the brain as the most relevant tissue. BMI and metabolic traits should be considered as partly behavioural traits. The wall between 'behaviour genetics' and 'medical genetics' is much thinner than most suppose.

Pradeep Natarajan

@pnatarajanmd

28 days

Great work led by former co-postdoc @hongheeW ! Honored to contribute to this substantial effort led by him. @NatureGenet @injeong_shim @aklfahed @patrick_ellinor @ATorkamani

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Alex Strudwick Young

@AlexTISYoung

1 month

Very cool ancient DNA study on bronze age kefir from Xinjiang. I suspect that fermentation techniques - which reduce lactose - explain why lactase persistence didn't evolve rapidly across populations consuming dairy. Now we know more about the cultures and techniques of

Iosif Lazaridis

@iosif_lazaridis

1 month

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Alex Strudwick Young

@AlexTISYoung

4 years

Mendelian randomisation can be led astray by population stratification and assortative mating. This paper shows how genetic data on close relatives can be used to remedy this:

Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomiz...

Nature Communications - Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses....

www.nature.com

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Alex Strudwick Young

@AlexTISYoung

4 years

Explainer on new work (with Augustine Kong, the SSGAC, and others) detailing our method for imputing parental genotypes from sibling and parent-offspring data () to increase power for family based analyses. Software here () (1/n).

GitHub - AlexTISYoung/snipar: Imputation of parental genotypes, inference of sibling IBD segments,...

Imputation of parental genotypes, inference of sibling IBD segments, family based GWAS, and polygenic score analyses. - GitHub - AlexTISYoung/snipar: Imputation of parental genotypes, inference o...

github.com

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Alex Strudwick Young

@AlexTISYoung

7 years

Our article on the 'Nature of Nurture' out today in @sciencemagazine (), along with an article by @carlzimmer in the New York Times ().

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Alex Strudwick Young

@AlexTISYoung

1 year

Out today in Behavioral and Brain Sciences, @DamienMorris , @StuartJRitchie , and my response to @callie_h_burt 's critique of the use of genetic predictors in social science research: . We conclude: Burt is correct that social scientists should include

Tractable limitations of current polygenic scores do not excuse genetically confounded social...

Tractable limitations of current polygenic scores do not excuse genetically confounded social science - Volume 46

www.cambridge.org

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Alex Strudwick Young

@AlexTISYoung

1 year

@razibkhan I wonder how many of the academics speaking out against the removal of Eisen would do so for a right-wing academic who said something offensive to left wing orthodoxy. My guess: almost none of them.

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Alex Strudwick Young

@AlexTISYoung

6 years

My paper with @genemodeller on finding genetic effects on phenotypic variability with application to BMI in UK Biobank out today in @NatureGenet . Short accessible blog here: . Software freely available here:

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Alex Strudwick Young

@AlexTISYoung

3 years

A lot of people made (spurious) criticisms of plots showing years of education (EA) against our predictor, the EA4 PGI, due to the lumpy distribution of EA. So here's a bonus unpublished plot with a less lumpy outcome variable, Average English & Maths GCSE grades from MCS. 🧵

Alex Strudwick Young

@AlexTISYoung

3 years

Twitter messed up the uploading of the plots. Here is the plot showing EA (y-axis) against PGI (x-axis):

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Alex Strudwick Young

@AlexTISYoung

4 years

Nice paper adding to the evidence that controlling for principal components is not sufficient to remove confounding from GWAS

Abdel Abdellaoui

@dr_appie

4 years

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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Alex Strudwick Young

@AlexTISYoung

6 months

Nothing has unified the accounts on my Twitter feed more than dunking on Huberman's misunderstanding of basic probability theory.

Matthew B Jané

@MatthewBJane

6 months

If you flip a coin twice, the chance you get heads at least once is 50%+50%=100%. If you flip a coin three times, it would be 150%, but that is a whole other thing…

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Alex Strudwick Young

@AlexTISYoung

2 years

This is greatly overstated. While BMI is an imperfect measure of adiposity, it is often the only measure available in many datasets. This is because height and weight are nearly always measured and things like waist circumference are not. Should we throw all of that data out? No

Peter Tennant has moved to Bluesky

@PWGTennant

2 years

My request for 2023: stop using BMI. If you're a member of the public, using it to suggest an 'ideal' weight: STOP. If you're a clinician, using it to judge someone's weight: STOP. If you're a scientist, using it as a proxy for adiposity: STOP. #StopUsingBMI #EpiTwitter

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Alex Strudwick Young

@AlexTISYoung

10 days

New work from Richard Border and others (including myself and @andywdahl ) that develops a computationally efficient software package, xftsim, for forward simulation of complex intergenerational dynamics including both genetic and cultural transmission from parents to offspring.

bioRxiv Genetics

@biorxiv_genetic

10 days

Simple models of non-random mating and environmental transmission bias standard human genetics statistical methods #biorxiv_genetic

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Alex Strudwick Young

@AlexTISYoung

8 years

Launching my website where I will blog on statistical genetics: . First series on interactions. #genetics #statistics

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Alex Strudwick Young

@AlexTISYoung

2 years

As descendants of early Neolithic farmers who spread into Europe from the near east, the Sardinians' ancestors have been in Europe for thousands of years longer than the Sami. But only the Sami are indigenous? This idea is an American import that doesn't work in Europe.

Sweden in EU

@SwedeninEU

2 years

Today is #SamiNationalDay ! The Sami are the EU’s only indigenous people. Since time immemorial, they have lived in an area stretching across parts of four countries: Finland, Norway, Sweden and Russia. This area is called Sápmi.

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Alex Strudwick Young

@AlexTISYoung

2 years

New work led by @OmanGuan , and presented this morning at #ASHG22 , on novel estimators for family-based GWAS that increase power and robustness: . We introduce two novel estimators that maximize power for estimating direct effects in different situations. 🧵

Novel estimators for family-based genome-wide association studies increase power and robustness

A goal of genome-wide association studies (GWASs) is to estimate the causal effects of alleles carried by an individual on that individual (‘direct genetic effects’). Typical GWAS designs, however,...

www.biorxiv.org

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Alex Strudwick Young

@AlexTISYoung

2 years

Our recent work on imputing missing parental genotypes for family-based genetic association analyses has been featured as a research highlight in Nature Methods, featuring an interview with myself and Augie Kong.

Nature Methods

@naturemethods

2 years

Research Highlight by Lin Tang: researchers describe a statistical method that imputes parental genotypes for accurate estimation of direct genetic effects driving genotype-phenotype associations. @NatureGenet paper: Highlight:

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Alex Strudwick Young

@AlexTISYoung

15 days

Thanks for a nice writeup @SashaGusevPosts ! A few comments: 1. "Though, it is worth noting, the family GWAS can also introduce some biases by effectively only testing the children of heterozygous parents at each variant (see: [Veller, Przeworski, Coop, (2024)] for more), or

Sasha Gusev

@SashaGusevPosts

15 days

I wrote a bit about the two very interesting studies of siblings/families from last week. Tan et al. family GWAS () and Sidorenko et al. sibling heritability estimates (). A few surprising findings summarized here: 🧵

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Alex Strudwick Young

@AlexTISYoung

2 years

Feldman states "there’s no reason to think these statistical correlations have any causal meaning", referring to correlations between education and education PGS. However, Feldman wrote a paper showing within-family analyses can recover causality () (1/4)

The New York Review of Books

@nybooks

2 years

Kathryn Paige Harden and others respond to M.W. Feldman and Jessica Riskin’s review of her book, “The Genetic Lottery.”

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Alex Strudwick Young

@AlexTISYoung

1 year

Further thoughts: The paper has two major contributions: 1) Construction of a large genealogical database on 422,374 people born in England between 1600 and 2022 along with measures of social status — occupational status, higher education status, literacy, dwelling value,

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Alex Strudwick Young

@AlexTISYoung

8 months

@MatthewBJane There needs to be a name for this phenomenon: regression denialism? Correlation denialism?

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Alex Strudwick Young

@AlexTISYoung

2 years

Critics of education GWAS say common variants have tiny effects and no obvious biological function. Point them to genes that have large effects, and they'll say they're just mutation intolerant genes that affect everything. Is there any type of genetic variant they like?

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Alex Strudwick Young

@AlexTISYoung

4 years

Happy to announce that I have started a new position at UCLA with @Dan_J_Benjamin at the Anderson School of Management and the Human Genetics department.

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Alex Strudwick Young

@AlexTISYoung

2 years

@ent3c @Quillette So you're saying that several articles that have found a detectable decline in the average polygenic score, including one I was involved in published in PNAS and covered in the Guardian (), are fringe science?

Natural selection making 'education genes' rarer, says Icelandic study

Researchers say that while the effect corresponds to a small drop in IQ per decade, over centuries the impact could be profound

www.theguardian.com

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Alex Strudwick Young

@AlexTISYoung

5 years

Final version of my opinion piece on 'Solving the missing heritability problem' is in @PLOSGenetics . Here's a related podcast I did hosted by @razibkhan :

The Insight: Solving the Missing Heritability

Razib talks to Alexander Young on whether the missing heritability is solved, and what it is in the first place

insitome.libsyn.com

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Alex Strudwick Young

@AlexTISYoung

1 year

A great example of how a socially mediated behavior (smoking) is affected by genetic variation. The variants that disrupt CHRNB2 protect against smoking and therefore against emphysema, COPD, and lung cancer. The boundary between behavioral and biomedical genetics is a construct

Veera Rajagopal 

@doctorveera

1 year

Thrilled to share our human genetics discovery of the protective association between rare variants in CHRNB2 (encoding a subunit of nicotinic acetylcholine receptors) and smoking addiction, now out in @NatureGenet . See the reply for a detailed thread. Below is a short summary.

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Alex Strudwick Young

@AlexTISYoung

1 year

I read this paper by @_twolfram and @DamienMorris in more detail recently. It's a worthwhile read for anyone interesting in intergenerational educational inequalities, (missing) heritability, and assortative mating. The paper applies an extended twin and family design (ETFD)

Damien Morris

@DamienMorris

1 year

My paper with @_twolfram is out in NPJ Science of Learning! We find that estimates of shared environmental influence for educational attainment in conventional twin studies may exaggerate the differences in educational opportunity between families: 🧵1/21

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Alex Strudwick Young

@AlexTISYoung

1 year

This is a bad decision by @eLife . To police the political opinions of editors to such an extreme degree will have a further chilling effect on a scientific culture that is already broken when it comes to free and open debate.

Michael Eisen

@mbeisen

1 year

I have been informed that I am being replaced as the Editor in Chief of @eLife for retweeting a @TheOnion piece that calls out indifference to the lives of Palestinian civilians.

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Alex Strudwick Young

@AlexTISYoung

2 years

I was looking at my Google Scholar (sad, I know) and I noticed that there is a rough inverse relationship between the effort I put into a paper and the citation rate. My most highly cited paper was a blog post that got turned into a paper. Has anyone else noticed this?

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Alex Strudwick Young

@AlexTISYoung

2 years

This editorial () proposes to "refuse publication of (or retract post-publication)" on grounds that are so vague and subjective they could be argued to apply to almost anything, including...(1/2)

Science must respect the dignity and rights of all humans

Nature Human Behaviour - New ethics guidance addresses potential harms for human population groups who do not participate in research but may be harmed by its publication.

www.nature.com

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Alex Strudwick Young

@AlexTISYoung

1 year

This is a nice paper (that I reviewed) that shows how an econometrics method, ORIV (obviously related instrumental variables), can be used to adjust for measurement error in analyses of genetic predictors (PGIs). PGIs are computed from GWAS summary statistics, which estimate

Rita Dias Pereira

@RitaDiasPereira

1 year

Our paper “Overcoming attenuation bias in regressions using polygenic indices” is out in @naturecomms 😊A thread!

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Alex Strudwick Young

@AlexTISYoung

3 years

An important analysis that shows the association between (non-transmitted) parental genotype and offspring education is perhaps not primarily due to 'genetic nurture', and is at least in part due to population structure/assortative mating.

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Alex Strudwick Young

@AlexTISYoung

1 year

Unless you stop people from accessing their genomic data, regulating pgs will be impossible. There will be web tools hosted outside the US where one can upload one's data to compute pgs. All regulation will achieve is increased costs to providers based in the US.

Shai Carmi

@ShaiCarmi

1 year

A proposal that the FDA should regulate direct-to-consumer delivery of polygenic scores. In my opinion this is not convincing. What is the evidence that consumers are harmed? Why should this be a priority for the FDA and worthy of their efforts?

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Alex Strudwick Young

@AlexTISYoung

3 years

With @razibkhan , I discuss heritability, the genetics of education, and some of the criticisms made of behavior genetics in the wake of @kph3k book, The Genetic Lottery.

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Alex Strudwick Young

@AlexTISYoung

5 years

From January, I will be working in LA with the SSGAC (). We're hiring a statistical genetics postdoc (). Come work with me, @Dan_J_Benjamin , @patrickaturley , and others at the frontier of social science genetics. Please retweet!

The SSGAC

The SSGAC is a cooperative enterprise among medical researchers and social scientists that coordinates genetic association studies for social science outcomes and provides a platform for interdisci...

www.thessgac.org

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Alex Strudwick Young

@AlexTISYoung

8 months

Exciting new work from @qinqin_huang @EmilieWigdor @hilsomartin and others (myself included): 'Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions'. 🧵 While it is understood that both rare mutations (often de-novo) and common variants

Emilie Wigdor

@EmilieWigdor

8 months

1/ We’re excited to share our new preprint “Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions” available on medRxiv!

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Alex Strudwick Young

@AlexTISYoung

2 years

@jew_AndAhalfMen That's certainly part of it but I think attitudes to alcohol have changed too. Perhaps part of it is not wanting photos of you as a drunken mess appearing on social media.

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Alex Strudwick Young

@AlexTISYoung

1 year

@SashaGusevPosts @charlesmurray If you're using the pgs as a measure of total genetic effect, that's not valid reasoning. I'm not sure where else you get the less than 20% number from.

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Alex Strudwick Young

@AlexTISYoung

3 years

Thoughtful review of @kph3k ’s The Genetic Lottery. There’s much I agree with, but I would give more credit to genomic methods in strengthening the argument that genetic factors play a causal role in social inequalities and that it is not all ‘red hair gene’ type effects (1/2).

Graham Coop

@Graham_Coop

3 years

. @molly_przew and I wrote a review of @kph3k ’s book, The Genetic Lottery: Why DNA matters for social equality, for @journal_evo : [pdf: ] 1/6

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Alex Strudwick Young

@AlexTISYoung

5 months

@vsbuffalo GWAS Consortium authors do well on these metrics

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Alex Strudwick Young

@AlexTISYoung

6 years

Heritability of longevity could be lower than believed on the basis of twin studies and analysis of pedigrees (). Great to see models including both assortative mating and cultural transmission applied to such a huge pedigree dataset.

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Alex Strudwick Young

@AlexTISYoung

2 years

@matias_kaplan

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Alex Strudwick Young

@AlexTISYoung

2 years

Review of 15 years of GWAS discovery by @dr_appie , @LoicYengo , Karin Verweij, and Peter Visscher:

15 years of GWAS discovery: Realizing the promise

We review how GWAS facilitated an impressive range of discoveries impacting multiple fields, including epidemiology, social science, and medicine. We predict that GWAS will continue to expand to more...

www.cell.com

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Alex Strudwick Young

@AlexTISYoung

1 year

Temple Crag. Eastern Sierras. (Big pines lake trail.)

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Alex Strudwick Young

@AlexTISYoung

13 days

Thanks to @SashaGusevPosts , we noticed an error in the publicly available summary statistics for age at first birth, where only the first four chromosomes were available. This has now been fixed and the full summary statistics for age at first birth are available to download.

Alex Strudwick Young

@AlexTISYoung

21 days

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Alex Strudwick Young

@AlexTISYoung

2 years

I wrote a blog post that is relevant to the discussion on non-additive effects: . Basically, most variance will be additive unless you have a non-monotonic genotype phenotype map (e.g. overdominance) that leads to zero or very small additive effects. This

Interactions in Genetics II: Epistasis and Dominance

This is the second part of a series of posts on interactions in genetics. In this post, we look at interactions between genetic variants, where those interactions can either be within loci (dominan…

geneticvariance.wordpress.com

Alex Strudwick Young

@AlexTISYoung

2 years

Comprehensive analysis of dominance (non-additive) effects in UK Biobank () finds negligible non-additive variance from common variants. However, it also finds that variants with large effects or phenotypes whose genetic architecture is dominated by a small

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Alex Strudwick Young

@AlexTISYoung

6 years

Would be curious to see a within-family analysis using siblings done on the results of this paper. That would test the contribution of population stratification, indirect genetic effects, and assortative mating -- all likely to be substantial. Plenty of siblings in UKB.

W David Hill

@WDavidHill

6 years

Our new GWAS on household income in the UK. New loci and genes identified, as well as links to tissue/cell types and other traits. @EdinburghUni @genscot @JulienBryois @nm_davies @StuartJRitchie @uk_biobank

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Alex Strudwick Young

@AlexTISYoung

4 years

Nice post explaining bias in GWAS effect estimates. I would add that an important source of 'genetic stratification' is assortative mating, which can lead to potentially very large bias in marginal effect estimates. (1/2)

Arslan Zaidi

@A_A_Zaidi

4 years

A general model for the bias in variant effect sizes due to population stratification: Thanks to @trang1618 for feedback!

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Alex Strudwick Young

@AlexTISYoung

20 days

@cremieuxrecueil @NatureGenet I think it's maybe harsh to blame the reviewers since this is a tricky technical issue that no one realized was potentially a problem until me, as far as I'm aware. The issue is that people got used to doing standard gwas and using low quality imputed genotypes is fine for

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Alex Strudwick Young

@AlexTISYoung

4 years

Interesting work furthering the argument that stratification needs to be taken more seriously in human genetics than simply using PCs or mixed models. Aligns with my recent anlyses of family data, which are consistent with a substantial contribution from stratification to GWAS.

Arslan Zaidi

@A_A_Zaidi

4 years

We (with @mathiesoniain ) have been thinking a lot about the effects of population stratification, especially on polygenic scores over the last year. Thrilled to finally share some findings (TL; DR):

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Alex Strudwick Young

@AlexTISYoung

1 year

I agree that EA displays the most confounding issues out of any well-studied phenotype. However, the difference with other traits is one of degree, not kind. Social science genetics has taken the issue of confounding seriously and studied it extensively. Other subfields often

Sasha Gusev

@SashaGusevPosts

1 year

A 🧵 on educational attainment (EA) GWAS and evidence of extensive confounding from multiple recent studies (much more than for disease traits). FWIW: I’m not a behavioral geneticist and I welcome disagreement on this.

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Alex Strudwick Young

@AlexTISYoung

1 year

A great thread on the FTO locus, which harbors a common variant with a strong effect on BMI and obesity. My take on this: GWAS reveals meaningful human biology, but that biology can be complex and take a lot of effort to work out, and it may be quite different in humans than in

Veera Rajagopal 

@doctorveera

1 year

Buckle up! We're in for a wild ride today. A new @NatMetabolism paper by scientists from China adds a surprising twist to the long-known FTO GWAS story. The FTO locus (16q12.2) is the first ever GWAS locus to be associated with obesity and even after 16 yrs now, scientists

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Alex Strudwick Young

@AlexTISYoung

1 month

The exome sequencing plus imputation pipeline developed by Regeneron is impressive in its efficiency for discovering genetic associations that are potential drug targets. But there is something to be said for having the complete genome sequences of all participants in a biobank

Regeneron Genetics Center

@RegeneronDNA

1 month

Whole genome sequencing (WGS) and whole exome sequencing (WES) have championed genomic discovery, but how do they compare? Published in @Nature , our team analyzed ~150K @uk_biobank participants to study WGS vs. WES, and their impacts on discovery in genetic association studies.

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Alex Strudwick Young

@AlexTISYoung

6 years

Interesting results on 'genetic nurture' and how to interpret the effects of polygenic scores: . Estimates of direct effects of educational attainment, cognitive ability, and depression polygenic scores less than half the size of the standard estimates.

Genetic Nature or Genetic Nurture? Quantifying Bias in Analyses Using Polygenic Scores

Summary statistics from a genome-wide association study (GWAS) can be used to generate a polygenic score (PGS). For complex, behavioral traits, the correlation between individual PGS and phenotype...

www.biorxiv.org

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Alex Strudwick Young

@AlexTISYoung

9 months

This should also be true if you want to stay in academia.

Jordan Nafa

@ajordannafa

9 months

If you're at all interested in leaving academia post-PhD, every paper you write should have a corresponding github repo. Super simple way of demonstrating to future employers you actually know how to do things

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Alex Strudwick Young

@AlexTISYoung

4 years

Lecture I gave at Berkeley on 'Disentangling Nature and Nurture Using Genomic Family Data'

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Alex Strudwick Young

@AlexTISYoung

3 years

A polygenic index is a weighted sum of many SNP genotypes, so will be approximately normally distributed in general (provided the weights are somewhat evenly spread). This doesn't automatically imply anything about the phenotype distribution in the population.

Mike White

@genologos

3 years

This is not merely an attack on social science genetics - it’s a dismissal of genetics in general as a hopelessly subjective endeavor. And when traits are normally distributed - well that’s what those bad eugenicists thought!

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Alex Strudwick Young

@AlexTISYoung

2 years

Excited to be visiting the Institute for Behavior Genetics at UC Boulder today!

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Alex Strudwick Young

@AlexTISYoung

7 years

New series of blog posts on heritability and its estimation. First: what is heritability? #genetics

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Alex Strudwick Young

@AlexTISYoung

4 years

As detailed in our review paper (), standard GWAS estimates of SNP effects include contributions four distinct sources: the direct effect of inheriting an allele, indirect effects from relatives, population stratification, and assortative mating (2/n).

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Alex Strudwick Young

@AlexTISYoung

1 year

James Lee's commentary on @GregoryClarkUCD 's paper on the inheritance of social status is out in PNAS:

The heritability and persistence of social class in England | PNAS

The heritability and persistence of social class in England

www.pnas.org

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Alex Strudwick Young

@AlexTISYoung

6 years

Important results on stratification and its effects on both measures of selection and LD-score regression. LD-scores and population differentiation found to be correlated (likely due to background selection), casting doubt on it as a clean method for assessing stratification.

Graham Coop

@Graham_Coop

6 years

Updated preprint: Reduced signal for polygenic adaptation of height in UK Biobank. @JeremyJBerg , @arbelharpak , Nasa Sinnott-Armstrong et al @jkpritch

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Alex Strudwick Young

@AlexTISYoung

6 years

It has always been my intuition that individuals or small groups are more likely to produce truly novel science than large teams. This study confirms this. I can't help but think of these huge GWAS consortia that do useful but rarely truly novel work

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Alex Strudwick Young

@AlexTISYoung

6 years

Excited to be moderating/facilitating a session at ASHG 2019 in Houston on 'Potential policy implications of genetic research on education' with four brilliant speakers: @kph3k , @daltonconley , @melindacmills , and @AysuOkbay . Also excited about the tacos and BBQ.

Kathryn Paige Harden

@kph3k

6 years

The invited program from @GeneticsSociety is up! Come to Texas, eat tacos & barbecue, & hear me, @daltonconley , @AysuOkbay , & @melindacmills talk about policy implications of genetic research on education.

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Alex Strudwick Young

@AlexTISYoung

2 years

A subtle point that this paper makes concrete is that confounding in the GWAS used to make a PGS complicates the interpretation of within-family estimates of PGS associations across traits: i.e., just because PGS of trait 1 predicts trait 2 within-family, that doesn't imply

Graham Coop

@Graham_Coop

2 years

New preprint by @carl_veller and myself on the interpretation of population and family-based genome-wide association studies in the presence of confounding

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Alex Strudwick Young

@AlexTISYoung

2 years

Here I was thinking it was just because they ate lots of fish.

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Alex Strudwick Young

@AlexTISYoung

5 months

@SpencrGreenberg My article on the missing heritability problem casts some light on twin estimates of heritability - as discussed here - in relation to more recent genomic data based estimates:

Solving the missing heritability problem

pmc.ncbi.nlm.nih.gov

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Alex Strudwick Young

@AlexTISYoung

1 year

@SashaGusevPosts @charlesmurray You are ignoring decades of twin and behaviour genetics research, though, and the substantial uncertainty in the RDR estimate as well as the fact SNP heritability isn't total heritability. I am inclined to think that twin studies have overestimated heritability, but to

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Alex Strudwick Young

@AlexTISYoung

3 years

Open letter, of which I'm a signatory, correcting the nonsense written in Scientific American about EO Wilson and his legacy.

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