Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels

Alzheimer's Research & Therapy
Taylor J MaxwellAlzheimer’s Disease Neuroimaging Initiative

Abstract

A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G. We performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping was used to assess significance. We found four significant tau/Aβ42 rQTL from three unique locations and six ptau/Aβ42 rQTL from five unique locations. G×G screens with these rQTL produced four significant G×G interactions (one Aβ42, two ptau, and one tau) with four rQTL where each second locus was from a unique location. On follow-up, rs1036819 and rs74025622 were associated with Alzheimer's disease (AD) case/control status; rs15205 and rs79099429 were associated with rate of decline. The two most significant rQTL (rs8027714 and rs1036819) for ptau/...Continue Reading

References

Jul 1, 1988·Annals of Neurology·J C MorrisL Berg
Jan 18, 2008·Genetic Epidemiology·Charles Kooperberg, Michael Leblanc
Mar 20, 2009·Annals of Neurology·Leslie M ShawUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Oct 1, 2009·Heredity·W-H WeiD-J de Koning
Feb 27, 2010·Annals of Neurology·John C MorrisMark A Mintun
Apr 14, 2010·Annals of Human Genetics·Petra BůžkováKenneth Rice
May 11, 2010·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Kazuhiko Nakabayashi, Senji Shirasawa
Nov 26, 2010·Proceedings. Biological Sciences·Mihaela PavlicevGünter P Wagner
Apr 5, 2011·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Mihaela PavlicevJames M Cheverud
Nov 23, 2011·Obstetrics and Gynecology·Kristina Allen-BradyPeggy A Norton
Jun 14, 2012·The Journal of Biological Chemistry·Lujia ZhouBart De Strooper
Jun 21, 2012·Genetic Epidemiology·Li HsuCharles Kooperberg
Jul 24, 2012·Human Molecular Genetics·Carlos CruchagaAlison M Goate
Jul 23, 2013·Genetic Epidemiology·W James GaudermanJuan Pablo Lewinger
Feb 28, 2014·Nature·Gibran HemaniJoseph E Powell
Mar 25, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Timothy J HohmanUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Aug 21, 2014·Frontiers in Aging Neuroscience·Timothy J HohmanUNKNOWN Alzheimer's Neuroimaging Initiative
Dec 24, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·UNKNOWN International Genomics of Alzheimer's Disease Consortium (IGAP)
Jan 17, 2015·EMBO Molecular Medicine·Yasuhiko KizukaNaoyuki Taniguchi
Jul 22, 2015·Neurotoxicity Research·Timothy J HohmanJulie A Schneider
Jul 16, 2016·Translational Neurodegeneration·Riqiang Yan
Jan 18, 2017·Annals of Clinical and Translational Neurology·Sarah A GaglianoMichael E Weale
Apr 28, 2017·Alzheimer's Research & Therapy·Yan-Shi HuJu Wang
Oct 1, 1997·Evolution; International Journal of Organic Evolution·Eric J Routman, James M Cheverud
Feb 27, 2018·Journal of Alzheimer's Disease : JAD·Jorge L Del-AguilaCarlos Cruchaga

❮ Previous
Next ❯

Citations

Jun 10, 2019·Journal of Alzheimer's Disease : JAD·Bin-Lu SunXiu-Qing Yao
Mar 1, 2021·Neurobiology of Aging·Bo-Hyun KimUNKNOWN Alzheimer's Disease Neuroimaging Initiative

❮ Previous
Next ❯

Methods Mentioned

BETA
chip

Software Mentioned

PLINK
R
GERAD
Julia
nlme
IMPUT2
EADI
CHARGE

Related Concepts

Related Feeds

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Autoimmune Thyroiditis

Autoimmune thyroiditis is an inflammatory disease of thyroid gland due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-cells and thyroid autoantibodies. Discover the latest research on autoimmune thyroiditis here.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.

Researcher Network:CZI Neurodegeneration Challenge

The Neurodegeneration Challenge Network aims to provide funding for and to bring together researchers studying neurodegenerative diseases. Find the latest research from the NDCN grantees here.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.