Challenges in phenotype definition in the whole-genome era: multivariate models of memory and intelligence

Sabb, Fred W.; Burggren, Alison C.; Higier, Rachel G.; Fox, J.; He, Jialin; Parker, D. Stott; Poldrack, Russell A.; Chu, Wesley W.; Cannon, Tyrone D.; Freimer, Nelson B.; Bilder, Robert M.

doi:10.1016/j.neuroscience.2009.05.013

Cited by 57 publications

(44 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first generation of GWA studies have indicated that traditional psychiatric diagnostic phenotypes might not provide the most powerful means of mapping disease loci (Sabb et al, 2009). It is becoming increasingly apparent that within diagnostic categories, such as bipolar disorder and schizophrenia, extensive aetiological and genetic heterogeneity operates (O'Donovan et al, 2009).…”

Section: Phenotypic Refinementmentioning

confidence: 99%

Alzheimer's disease genetics: current knowledge and future challenges

Hollingworth

Harold

Jones

et al. 2010

Int J Geriat Psychiatry

View full text Add to dashboard Cite

Alzheimer's disease (AD) is highly heritable, but genetically complex. Recently, three large-scale genome-wide association studies have made substantial breakthroughs in disentangling the genetic architecture of the disease. These studies combined include data from over 43 000 independent individuals and provide compelling evidence that variants in four novel susceptibility genes (CLU, PICALM, CR1, BIN1) are associated with disease risk. These findings are tremendously exciting, not only in providing new avenues for exploration, but also highlighting the potential for further gene discovery when larger samples are analysed. Here we discuss progress to date in identifying risk genes for dementia, ways forward and how current findings are refining previous ideas and defining new putative primary disease mechanisms.

show abstract

Section: Phenotypic Refinementmentioning

confidence: 99%

Alzheimer's disease genetics: current knowledge and future challenges

Hollingworth

Harold

Jones

et al. 2010

Int J Geriat Psychiatry

View full text Add to dashboard Cite

show abstract

“…In their review, Sabb et al (2009) concluded that genetic associations had thus far accounted for only about 7% of the variance in a variety of memory measures.…”

mentioning

confidence: 99%

Genetic complexity of episodic memory: A twin approach to studies of aging.

Kremen

Panizzon

Franz

et al. 2014

Psychology and Aging

View full text Add to dashboard Cite

Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if “memory is memory” and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory.

show abstract

“…Although the first-generation GWAS in AD indicated that psychiatric and cognitive function used as endophenotypes do not provide a powerful means of mapping disease loci [27,28], which was not completely a surprise given the extensively negative results of GWAS in several psychiatric disorders [29,30], the incorporation of clinical and neuropathological information into GWAS has proven successful. Several studies have now reported on data from the ADNI (Alzheimer's Disease Neuroimaging Initiative) database, which is ideal for endophenotype studies in AD, since it brings together MRI (magnetic resonance imaging), PET (positron emission tomography), genetic factors, other biological markers and clinical and neuropsychological assessments of the same samples.…”

Section: Brief Overview Of Ad Genetics: Focus On the Recent Gwas Resultsmentioning

confidence: 99%