Aoxing Liu
@Aoxing2
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postdoc with @dalygene at Broad Institute & MGH; Geneticist - learning why, how, and when cells made “detectable” errors with large biobanks!
Boston, MA
Joined May 2018
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Pinned Tweet
New out in Nature!!
With age, women can lose one X chromosome in their leukocytes.
What’s the cause/consequence?
How does it differ from the loss of the Y chromosome in men?
@broadinstitute
@FinnGen_FI
@FIMM_UH
@theNCI
@Cambridge_Uni
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101
332
New preprint!
10% of women lose one X chromosome in a fraction of leukocytes. What’s the cause/consequence?
We leveraged genetic data from 904,524 women and show germline variants predispose to mLOX and shape the magnitude of clonal expansion.
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1/5
Our work on the relationship between diseases and childlessness is finally out in
@NatureHumBehav
!
The paper:
Our interactive dashboard:
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Hi - I will give a seminar about our recently published Nature paper on “mosaic X chromosome loss” at the PQG working group NEXT TUESDAY!
Welcome to Join the talk and discussion in person!!
⏰Time: 1-2 PM, Tuesday, Oct 22
🏠Location: Biostats Conference Room (2-426), Harvard
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Thanks,
@SafiaDanovi
, for a lovely "Research Highlight" in Nature Genetics about our "understanding X chromosome loss"!! 🧬🧬🧬
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Happy to have my work recognized by
@FinnGen_FI
and share the prize with
@mpreeve
!
Together, we are learning more about female genetics!!
🏄♀️🏄♀️🏄♀️
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New work about the Finnish pedigree and autoimmune diseases from
@feiyi_wang
, co-supervised by me,
@andganna
, and
@TinskuT
!
Preprint:
T1D and other autoimmune diseases (AIDs) co-occur in families. How parental AIDs impact T1D risk in offspring and how much of the familial risk is explained by HLA and non-HLA variants? 👩🏻🦱🧔🏻♂️👶🏻
Find out more from this thread 🧵 and our new preprint ⬇️!
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@andganna
@melindacmills
@akimova_eva
@XuejieDing
@DrSakari
@pecsi_max
@i_am_dr_doom
@FallTove
5/5
I have learned so many things through this journey 🛣️🛴🛶🛵🦽🚗🛸 from co-authors and from the research work itself !
The most important one I want to share is - research and life have ups and downs; be bold, be strong, and be persistent if you know what you want to achieve!!
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Thanks
@JaraCarcel
for the kind invitation & organization!! 💡💡💡
Looking forward to talking about sex chromosomes and sex differences with "The Biological Sex Differences in Stroke Working Group" from
@StrokeGenetics
!!
🧬🧬🧬
🚨 Exciting event! The Biological Sex Differences in Stroke Working Group from
@StrokeGenetics
is hosting a talk by Dr. Aoxing Liu (
@Aoxing2
) on her study, "Genetic Drivers and Cellular Selection of Female Mosaic X Chromosome Loss," recently published in
@Nature
. 🧬✨
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Kudos to our amazing collaborators!!! Mosaic X loss is such a fantastic and mysterious phenotype! This project would be impossible without your continuous support (💖💯🌟) during the last two years!!!
A preprint detailing our investigation of germline contributors to mosaic loss of the X chromosome (
#mLOX
) in 900K females is online! Check out this 🧵 by
@Aoxing2
summarizing our findings. Kudos to our amazing collaborators!
#NCI_ITEB
@NCIEpiTraining
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10/10
We also got insightful advice and warm support from
@s_mccarroll
,
@dalygene
,
@ttukiainen
,
@HannaMOllila
@bloodgenes
and many others not on Twitter!!
0
0
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1/10
Why do women develop mosaic loss of X (mLOX)?
Detectable age-related mLOX develops in females only if the mutant haematopoietic stem cell survives X loss and the loss confers a proliferative advantage, resulting in a mosaic of normal cells and cells with X loss.
1
0
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7/10
We put together an amazing team co-led by
@Aoxing2
,
@mitchiela
,
@jrbperry
,
@andganna
, Po-Ru Loh, and
@freeseek82
(developer of the scalable MoChA pipeline (…))!!
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4/10
Which X chromosome copy is lost?
We identified 44 independent chromosome X germline variants for which one allele is preferentially lost. Most of these variants were associated with blood cell phenotypes.
1
0
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9/10
This project is a global effort! Kudos to our fantastic collaborators!!
@FinnGen_FI
,
@ESTbiobank
,
@uk_biobank
, biobank Japan, BCAC, MVP, MGB, PLCO.
@ChikashiTerao
,
@BRGorman
,
@m_reedik
,
@AlexBickMDPhD
,
@pnatarajanmd
,
@WeiyinZ
,
@ndfreedman
,
@NCIChanock
,
@APalotie
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3/10
Are genetic drivers of mLOX shared with mosaic loss of the Y chromosome (mLOY) in men?
Only a small fraction of associations were shared between mLOX and mLOY (genetic correlation=0.3), suggesting partially different biological processes.
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6/10
What are the clinical consequences of mLOX?
Out of 1,253 diseases examined, women with mLOX had an elevated risk of myeloid and lymphoid leukemias and pneumonia. Associations with leukemia risk remained when ruling out the effects of other types of clonal hematopoiesis.
1
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5/10
Can we predict which X chromosome is retained in expanded clones?
A differential polygenic score including 44 independent X chromosome allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile.
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(9) This project is a global effort! Kudos to our fantastic collaborators!
@FinnGen_FI
,
@ESTbiobank
,
@uk_biobank
, biobank Japan, BCAC, MVP, MGB, PLCO,
@ChikashiTerao
,
@BRGorman
,
@m_reedik
,
@AlexBickMDPhD
,
@pnatarajanmd
,
@WeiyinZ
,
@ndfreedman
,
@NCIChanock
,
@APalotie
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4/5
I am so lucky to have had this journey with the fantastic team - amazing 💯
@andganna
&
@melindacmills
for co-leading the work, 🫶
@akimova_eva
,
@XuejieDing
,
@DrSakari
,
@pecsi_max
,
@i_am_dr_doom
,
@FallTove
& many others for your endless supports both as co-authors and friends!
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(6) What are clinical consequences of mLOX?
Out of 1,253 diseases examined, women with mLOX had an elevated risk of myeloid and lymphoid leukemias and pneumonia. Associations with overall leukemia risk remained when ruling out the effects of other types of clonal hematopoiesis.
1
0
5
(7) We put together an amazing team co-led by
@mitchiela
,
@jrbperry
,
@andganna
, Po-Ru Loh, and
@freeseek82
(developer of the scalable MoChA pipeline ())!
1
0
5
2/10
What role do germline mutations play?
Studying 880K women of European or East Asian ancestry, we identified 56 common variants and FBXO10 missense variants influencing mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition, and autoimmunity.
1
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(Email Amanda King (amking
@hsph
.harvard.edu) and cc me (liuaoxin
@broadinstitute
.org), if anyone needs a guest pass to get into HSPH!)
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(3) Are genetic drivers of mLOX shared with mosaic loss of the Y chromosome (mLOY) in men?
Only a small fraction of associations were shared between mLOX and mLOY (rg=0.30), suggesting different biological processes. Interestingly, some HLA signals showed inverse associations.
1
0
4
8/10
With great help from
@ZhaoDylan
(rare variant),
@MattiPirinen
(Bayesian line model),
@zekavatm
(pheWAS),
@aikat33
(GWAS to gene),
@ZhiyuHas0Memory
(genetic correlation), Kai Yu (pathway),
@DrFlashHeart
(association with leukemia), and
@DerekWBrown_1
in post-analyses!!
1
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2/5
University of Oxford press release:
FIMM’s news story:
Leverhulme Centre for Demographic Science news:
The BBC interview ratio (listen from 16:55):
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It's a four year journey:
We started by applying about 20 registers from different 🇫🇮 & 🇸🇪 data agencies, went through endless data QC, tried our best to fully use large sample size!
We also learned how sensitive this topic is with 58 pages of peer-reviewed information! 🧐
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Congratulations
@ZhiyuHas0Memory
! Hope this paper will be a GOOD “memory” for you! :)
Is the genetic of disease susceptibility and progression shared?
We look at this question within a global biobank collaboration across 10 major diseases 💁
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(5) Can we predict which X chromosome is retained in expanded clones?
A differential polygenic score including 44 independent X chromosome allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile.
1
0
3
(8) With great help from
@ZhaoDylan
(rare variant),
@MattiPirinen
(Bayesian model),
@zekavatm
(pheWAS),
@aikat33
(GWAS to gene), Zhiyu Yang (genetic correlation), Kai Yu (pathway analysis),
@DrFlashHeart
(association with leukemia) and
@DerekWBrown_1
in post-GWAS analyses!
1
0
3
(1) Why do women develop mLOX?
Detectable age-related mosaic loss of X (mLOX) develops in females only if the mutant haematopoietic stem cell (HSC) survives mLOX and the mutation confers a proliferative advantage, resulting in a mosaic of normal cells and cells with X loss.
2
0
2
(4) Which X chromosome copy is lost?
We identified 44 independent chromosome X germline variants for which one allele is preferentially lost. Most of these variants were associated with blood cell phenotypes.
1
0
2
(2) What role do germline mutations play?
Studying 900K women of European or East Asian ancestry, we identified 49 common variants and FBXO10 missense variants influencing mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition, and autoimmunity.
1
1
2
(10) We also got great advices/supports from
@s_mccarroll
,
@dalygene
,
@ttukiainen
,
@HannaMOllila
,
@bloodgenes
and many others who not on Twitter!
0
0
2
0
0
1
@MartinKolk
@andganna
@melindacmills
Hello, Martin, thanks for your interest in our work. We estimated N of children unborn related to disease diagnoses in the observational period by combining relative risk (converted from OR), disease prevalence, and parity. Please see table S8-9 in appendix p30-33.
0
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@XinAnnWang
@HarvardChanSPH
@HarvardBiostats
@dfcidatascience
@HarvardEpi
Many thanks,
@XinAnnWang
!! :)
0
0
1
@alanmej55130600
Hello,
@Tony_Chen6
&
@XinAnnWang
, I guess this question is for you - the organizers - are we going to have a Zoom link for people like
@alanmej55130600
who are not living in Boston? 🗺️ 😉😉😉
0
0
1
@ShihchengGuo
Hello,
@ShihchengGuo
, great question!!
As commented by
@SafiaDanovi
in the Nature Genetics Research Highlights () - "This study provides an important stepping stone for future investigations of mLOX and its role in female health and disease."
In other
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0
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TL;DR 🧬🧬🧬
@mpreeve
work on lichen planus -
My work on mosaic X loss -
The journal articles 📰📰📰
Lichen planus -
Mosaic X loss -
New out in Nature!!
With age, women can lose one X chromosome in their leukocytes.
What’s the cause/consequence?
How does it differ from the loss of the Y chromosome in men?
@broadinstitute
@FinnGen_FI
@FIMM_UH
@theNCI
@Cambridge_Uni
10
101
332
0
0
1