TY  - JOUR
T1  - UNtangling the genetics of a complex disease
AU  - Daly MJ
Y1  - 1998/08/19
N1  - 10.1001/jama.280.7.652
JO  - JAMA
SP  - 652
EP  - 653
VL  - 280
IS  - 7
N2  - 
In contrast to many of the struggles of complex trait linkage analysis,
Alzheimer disease (AD) research has provided a shining example of the successes
that are possible using the traditional study design that has provided the
bulk of the extensive genetic understanding of numerous monogenic diseases
such as cystic fibrosis and Huntington disease. In recent years, 4 genes have
been identified that are involved in the heritable risk of AD. Mutations in
3 of these 4 (the amyloid precursor protein, presenilin 1, and presenilin
2 genes) cause an extremely rare, early-onset, highly penetrant, dominantly
acting form of the disease.1- 4
Although unlikely to be valuable in screening for AD, these rare mutations
provide important revelations about the biological mechanisms of AD. The fourth,
the ∊4 allele of the APOE gene,5
confers a roughly 3-fold increased risk of developing the common, later-onset
form of the disease. Because of its frequency (approximately 15% in the general
population), this allele accounts for nearly all of the currently identified
genetic risk associated with AD. It is clear, however, that other genetic
risk factors for the common form of AD must exist as these 4 factors account
for only 50% of the total genetic risk.6

SN  - 0098-7484
M3  - doi: 10.1001/jama.280.7.652
UR  - http://dx.doi.org/10.1001/jama.280.7.652
ER  -