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DTSTAMP:20250504T175643Z
DESCRIPTION:Zhonghua Liu\, PhD\n\nAssistant Professor\n	Department of Biosta
 tistics |\n	Columbia University\n\nWHEN: Monday\, September 23\, 2024\, fro
 m 3:30 to 4:30 p.m.\n	WHERE: Hybrid | 2001 51³Ô¹ÏÍøCollege Avenue\, Room 120
 1\; Zoom\n	NOTE: Zhonghua Liu will be presenting in-person\n\nAbstract\n\nH
 idden confounding bias is a major threat in identifying causal protein bio
 markers for Alzheimer’s disease in non-randomized studies. Mendelian rando
 mization (MR) framework holds the promise of removing such hidden confound
 ing bias by leveraging protein quantitative trait loci (pQTLs) as instrume
 ntal variables (IVs) for establishing causal relationships. However\, some
  pQTLs might violate core IV assumptions\, leading to biased causal infere
 nce and misleading scientific conclusions. To address this urgent challeng
 e\, we propose a novel MR method called MR-SPI that first Selects valid pQ
 TL IVs under the Anna Karenina Principle and then performs valid Post-sele
 ction Inference that is robust to possible pQTL selection error. We furthe
 r develop a computationally efficient pipeline by integrating MR-SPI and A
 lphaFold3 to automatically identify causal protein biomarkers and predict 
 protein 3D structural alterations. We apply this pipeline to analyze genom
 e-wide summary statistics for 912 plasma proteins in 54\,306 participants 
 from UK Biobank and for Alzheimer’s disease (AD) in 455\,258 samples. We i
 dentified seven proteins associated with Alzheimer's disease - TREM2\, PIL
 RB\, PILRA\, EPHA1\, CD33\, RET\, and CD55 - whose 3D structures are alter
 ed by missense genetic variations. This discovery offers novel insights in
 to their biological roles in AD development and may aid in identifying pot
 ential drug targets.\n\nSpeaker bio\n\nDr. Zhonghua Liu is currently Assis
 tant Professor in the Department of Biostatistics at Columbia University. 
 His primary research interests include causal inference\, semiparametric e
 fficiency theory\, machine (deep) learning theory and applications\, stati
 stical genetics/genomics\, causal mediation analysis\, Mendelian randomiza
 tion. He obtained his doctorate in Biostatistics from Harvard University a
 dvised by Professor Xihong Lin.\n
DTSTART:20240923T193000Z
DTEND:20240923T203000Z
SUMMARY:Integrating a novel robust Mendelian randomization method for prote
 omics data analysis and AlphaFold3 for predicting 3D structural alteration
 s
URL:/epi-biostat-occh/channels/event/integrating-novel
 -robust-mendelian-randomization-method-proteomics-data-analysis-and-alphaf
 old3-359642
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