Abstract
The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor (FGF20) in the survival of dopaminergic cells. FGF20 is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether FGF20 influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the FGF20 gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP, rs1989754 (P = .0006), and two SNPs, rs1721100 (P = .02) and ss20399075 (P = .0008), located in the 3′ regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (P = .0003), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (P = .0009). Our results strongly support FGF20 as a risk factor for PD.
| Original language | English |
|---|---|
| Pages (from-to) | 1121-1127 |
| Number of pages | 7 |
| Journal | American Journal of Human Genetics |
| Volume | 74 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. / Van Der Walt, Joelle M.; Noureddine, Maher A.; Kittappa, Raja; Hauser, Michael A.; Scott, William K; McKay, Ron; Zhang, Fengyu; Stajich, Jeffrey M.; Fujiwara, Kenichiro; Scott, Burton L.; Pericak-Vance, Margaret A; Vance, Jeffery M; Martin, Eden R.
In: American Journal of Human Genetics, Vol. 74, No. 6, 01.06.2004, p. 1121-1127.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease
AU - Van Der Walt, Joelle M.
AU - Noureddine, Maher A.
AU - Kittappa, Raja
AU - Hauser, Michael A.
AU - Scott, William K
AU - McKay, Ron
AU - Zhang, Fengyu
AU - Stajich, Jeffrey M.
AU - Fujiwara, Kenichiro
AU - Scott, Burton L.
AU - Pericak-Vance, Margaret A
AU - Vance, Jeffery M
AU - Martin, Eden R
PY - 2004/6/1
Y1 - 2004/6/1
N2 - The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor (FGF20) in the survival of dopaminergic cells. FGF20 is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether FGF20 influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the FGF20 gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP, rs1989754 (P = .0006), and two SNPs, rs1721100 (P = .02) and ss20399075 (P = .0008), located in the 3′ regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (P = .0003), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (P = .0009). Our results strongly support FGF20 as a risk factor for PD.
AB - The pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra of patients with Parkinson disease (PD) is poorly understood. Current research supports the involvement of fibroblast growth factor (FGF20) in the survival of dopaminergic cells. FGF20 is a neurotrophic factor that is preferentially expressed within the substantia nigra of rat brain. The human homologue has been mapped to 8p21.3-8p22, which is within an area of PD linkage revealed through our published genomic screen. To test whether FGF20 influences risk of PD, we genotyped five single-nucleotide polymorphisms (SNPs) lying within the FGF20 gene, in a large family study. We analyzed our sample (644 families) through use of the pedigree disequilibrium test (PDT), the genotype PDT, the multilocus-genotype PDT, and the family-based association test to assess association between risk of PD and alleles, genotypes, multilocus genotypes, and haplotypes. We discovered a highly significant association of PD with one intronic SNP, rs1989754 (P = .0006), and two SNPs, rs1721100 (P = .02) and ss20399075 (P = .0008), located in the 3′ regulatory region in our overall sample. Furthermore, we detected a haplotype (A-G-C-C-T) that is positively associated with risk of PD (P = .0003), whereas a second haplotype (A-G-G-G-C) was found to be negatively associated with risk of PD (P = .0009). Our results strongly support FGF20 as a risk factor for PD.
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U2 - 10.1086/421052
DO - 10.1086/421052
M3 - Article
VL - 74
SP - 1121
EP - 1127
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -