TY - JOUR
T1 - Neurocognitive impairment in type 2 diabetes
T2 - evidence for shared genetic aetiology
AU - Mollon, Josephine
AU - Curran, Joanne E
AU - Mathias, Samuel R.
AU - Knowles, Emma E.M.
AU - Carlisle, Phoebe
AU - Fox, Peter T.
AU - Olvera, Rene L.
AU - Göring, Harald H.H.
AU - Rodrigue, Amanda
AU - Almasy, Laura A
AU - Duggirala, Ravindranath
AU - Blangero, John C
AU - Glahn, David C.
N1 - Funding Information:
Financial support for this study was provided by the National Institutes of Health grants MH059490 (principal investigator [PI]: JB), MH078143 (PI: DCG), MH078111 (PI: JB), MH083824 (PIs: DCG/JB) and AG058464 (PIs: DCG/JB). The sponsors had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of this manuscript. Acknowledgements
Funding Information:
We are very grateful to all the participants of the GOBS study. We thank M. Woolsey (Research Imaging Institute, University of Texas Health Science Center at San Antonio, TX, USA) for her role in data collection.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Aims/hypothesis: Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition. Methods: Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery. Results: Negative phenotypic correlations (ρp) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]: ρp = −0.143, p = 0.001), verbal memory (California Verbal Learning Test [CVLT] recall: ρp = −0.111, p = 0.004) and face memory (Penn Face Memory Test [PFMT]: ρp = −0.127, p = 0.002; PFMT Delayed: ρp = −0.148, p = 2 × 10−4), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (ρg) were also observed between type 2 diabetes and measures of attention (CPT d′: ρg = −0.401, p = 0.001), working memory (digit span backward test: ρg = −0.380, p = 0.005), and face memory (PFMT: ρg = −0.476, p = 2 × 10−4; PFMT Delayed: ρg = −0.376, p = 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′: β = −0.219, p = 0.005), working memory (digit span backward: β = −0.326, p = 0.035), and face memory (PFMT: β = −0.171, p = 0.023; PFMT Delayed: β = −0.215, p = 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level. Conclusions/interpretation: These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease. Data availability: The data analysed in this study is available in dbGaP: www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2.
AB - Aims/hypothesis: Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition. Methods: Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery. Results: Negative phenotypic correlations (ρp) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]: ρp = −0.143, p = 0.001), verbal memory (California Verbal Learning Test [CVLT] recall: ρp = −0.111, p = 0.004) and face memory (Penn Face Memory Test [PFMT]: ρp = −0.127, p = 0.002; PFMT Delayed: ρp = −0.148, p = 2 × 10−4), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (ρg) were also observed between type 2 diabetes and measures of attention (CPT d′: ρg = −0.401, p = 0.001), working memory (digit span backward test: ρg = −0.380, p = 0.005), and face memory (PFMT: ρg = −0.476, p = 2 × 10−4; PFMT Delayed: ρg = −0.376, p = 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′: β = −0.219, p = 0.005), working memory (digit span backward: β = −0.326, p = 0.035), and face memory (PFMT: β = −0.171, p = 0.023; PFMT Delayed: β = −0.215, p = 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level. Conclusions/interpretation: These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease. Data availability: The data analysed in this study is available in dbGaP: www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2.
KW - Cognitive function
KW - Cognitive impairment
KW - Genetic correlation
KW - Genetic overlap
KW - Type 2 diabetes
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U2 - 10.1007/s00125-020-05101-y
DO - 10.1007/s00125-020-05101-y
M3 - Article
C2 - 32016567
AN - SCOPUS:85078962405
SN - 0012-186X
VL - 63
SP - 977
EP - 986
JO - Diabetologia
JF - Diabetologia
IS - 5
ER -