TY - JOUR
T1 - Genetic susceptibility to multiple sclerosis
T2 - Brain structure and cognitive function in the general population
AU - Ikram, Mohammad Arfan
AU - Vernooij, Meike W.
AU - Roshchupkin, Gennady V.
AU - Hofman, Albert
AU - van Duijn, Cornelia M.
AU - Uitterlinden, André G.
AU - Niessen, Wiro J.
AU - Hintzen, Rogier Q.
AU - Adams, Hieab H.H.
N1 - Publisher Copyright:
© 2016, © The Author(s), 2016.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Background: Multiple sclerosis (MS) affects brain structure and cognitive function and has a heritable component. Over a 100 common genetic risk variants have been identified, but most carriers do not develop MS. For other neurodegenerative diseases, risk variants have effects outside patient populations, but this remains uninvestigated for MS. Objectives: To study the effect of MS-associated genetic variants on brain structure and cognitive function in the general population. Methods: We studied middle-aged and elderly individuals (mean age = 65.7 years) from the population-based Rotterdam Study. We determined 107 MS variants and additionally created a risk score combining all variants. Magnetic resonance imaging (N = 4710) was performed to obtain measures of brain macrostructure, white matter microstructure, and gray matter voxel-based morphometry. A cognitive test battery (N = 7556) was used to test a variety of cognitive domains. Results: The MS risk score was associated with smaller gray matter volume over the whole brain (βstandardized = −0.016; p = 0.044), but region-specific analyses did not survive multiple testing correction. Similarly, no significant associations with brain structure were observed for individual variants. For cognition, rs2283792 was significantly associated with poorer memory (β = −0.064; p = 3.4 × 10−5). Conclusion: Increased genetic susceptibility to MS may affect brain structure and cognition in persons without disease, pointing to a “hidden burden” of MS.
AB - Background: Multiple sclerosis (MS) affects brain structure and cognitive function and has a heritable component. Over a 100 common genetic risk variants have been identified, but most carriers do not develop MS. For other neurodegenerative diseases, risk variants have effects outside patient populations, but this remains uninvestigated for MS. Objectives: To study the effect of MS-associated genetic variants on brain structure and cognitive function in the general population. Methods: We studied middle-aged and elderly individuals (mean age = 65.7 years) from the population-based Rotterdam Study. We determined 107 MS variants and additionally created a risk score combining all variants. Magnetic resonance imaging (N = 4710) was performed to obtain measures of brain macrostructure, white matter microstructure, and gray matter voxel-based morphometry. A cognitive test battery (N = 7556) was used to test a variety of cognitive domains. Results: The MS risk score was associated with smaller gray matter volume over the whole brain (βstandardized = −0.016; p = 0.044), but region-specific analyses did not survive multiple testing correction. Similarly, no significant associations with brain structure were observed for individual variants. For cognition, rs2283792 was significantly associated with poorer memory (β = −0.064; p = 3.4 × 10−5). Conclusion: Increased genetic susceptibility to MS may affect brain structure and cognition in persons without disease, pointing to a “hidden burden” of MS.
KW - Epidemiology
KW - genetics
KW - magnetic resonance imaging
KW - multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85033498202&partnerID=8YFLogxK
U2 - 10.1177/1352458516682104
DO - 10.1177/1352458516682104
M3 - Article
AN - SCOPUS:85033498202
SN - 1352-4585
VL - 23
SP - 1697
EP - 1706
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 13
ER -