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P3–166: PPARγ Pro12Ala genotype and cognitive function in older adults: Findings from the health ABC Study
Author(s) -
Yaffe Kristine,
Kanaya Alka,
Lindquist Karla,
Hsueh Wen-chi,
Harris Tamara,
Rosano Caterina,
Pope Sandra K.,
Li Rongling,
Newman Anne B.,
Cummings Steve R.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1434
Subject(s) - digit symbol substitution test , medicine , cognitive decline , allele , cognition , genotype , effects of sleep deprivation on cognitive performance , diabetes mellitus , type 2 diabetes , allele frequency , polymorphism (computer science) , dementia , disease , endocrinology , biology , psychiatry , genetics , pathology , alternative medicine , placebo , gene
matter hyperintensity (WMH) have estimated heritability between 0.550.73 among cognitively normal family members. Objective: Persons with and without AD are expected to have substantially different MRI phenotypes distributions. Our objective was to determine whether of MRI traits in siblings discordant for AD are heritable. Methods: We measured WMH, a rating of cerebrovascular disease (CVR) that reflects the WMH rating plus the number, size and location of infarcts if present, and general atrophy (GA) via MRI in 402 participants from 205 families, of the MIRAGE Study. Traits were rated on a 0-100 scale, and log-transformed to reduce skewness. Linear regression was used separately in cases and unaffected siblings to adjust for gender, age at first symptoms, and time from onset to MRI scan (cases), and gender and age at MRI (controls). We estimated heritability for the adjusted traits correcting for ascertainment by conditioning on the AD proband in each sibship using the variance components approach of SOLAR. Results: All three traits were significantly heritable. The heritability of CVR was 0.49 (SE 0.15, p 0.0004); WMH and GA had slightly lower heritability (h 0.32, 0.27, p 0.019, p 0.017). We used a measured genotype approach to test for differences in means of the adjusted transformed traits by the number of APOE 4 alleles. The number of 4 alleles was significantly associated with WMH (p 0.017, proportion of variance explained: 0.020). A trend toward association was observed also with CVR (p 0.070, proportion of variance explained: 0.011), but no association was observed with GA. Heritability of all measures remained significant after accounting for APO genotype, suggesting that a substantial portion of the genetic variation in these MRI traits remains to be explained by additional genes. Conclusions: The degree of degenerative change associated with AD is under genetic control. Identification of the genes involved may provide insights about pathogenesis.