Table 2: Stage one discovery phase results.
Sanger sequencing of four neighboring genes (NSF, KANSL1, SPPL2C, and CRHR1) located 900kb around MAPT on chromosome 17 identified 51 variants in 90 individuals clinically diagnosed with sporadic, late-onset Parkinson’s disease.
| Gene | Exon | Genotypes | rsID | Amino Acid | Mutation type | Frequency | r2 | Included in Stage 2 Genotyping |
|---|---|---|---|---|---|---|---|---|
| CRHR1 | 2 | C/T | rs12936511 | P20P | Synonymous | Common | <0.01 | N |
| CRHR1 | 6 | G/A | rs75638861 | V161M | Nonsynonymous | Common | <0.01 | Y |
| CRHR1 | 8 | T/C | rs16940665 | T252T | Synonymous | Common | 1 | N |
| CRHR1 | 10 | C/T | rs141817026 | C287C | Synonymous | Common | 1 | N |
| KANSL1 | 1 | C/T | rs200649587 | D10D | Synonymous | Rare | <0.01 | N |
| KANSL1 | 1 | A/C | rs17585974 | K104T | Nonsynonymous | Common | 0.83 | Y |
| KANSL1 | 1 | T/G | rs17662889 | L138L | Synonymous | Common | 0.86 | N |
| KANSL1 | 1 | G/T | rs149566146 | G191C | Nonsynonymous | Rare | <0.01 | Y |
| KANSL1 | 1 | A/G | rs144882998 | N207S | Nonsynonymous | Rare | 0.02 | Y |
| KANSL1 | 1 | A/G | rs141110759 | H212R | Nonsynonymous | Rare | <0.01 | Y |
| KANSL1 | 1 | C/T | rs17662853 | T221I | Nonsynonymous | Common | <0.01 | Y |
| KANSL1 | 1 | A/G | rs35643216 | N225D | Nonsynonymous | Common | 0.86 | Y |
| KANSL1 | 1 | C/T | rs1881194 | S232S | Synonymous | Common | 0.90 | N |
| KANSL1 | 1 | C/G | rs2240758 | S337S | Synonymous | Common | 0.01 | N |
| KANSL1 | 1 | A/G | rs1881193 | R247R | Synonymous | Common | 1 | N |
| KANSL1 | 3 | A/G | rs17576165 | P497P | Synonymous | Common | 1 | N |
| KANSL1 | 6 | G/C | rs191986791 | R619R | Synonymous | Rare | <0.01 | N |
| KANSL1 | 7 | G/A | rs2277613 | P712P | Synonymous | Common | <0.01 | N |
| KANSL1 | 7 | T/C | rs34043286 | S718P | Nonsynonymous | Common | 1 | N |
| KANSL1 | 10 | T/C | rs17574604 | F860F | Synonymous | Common | 1 | N |
| KANSL1 | 12 | C/T | rs35833914 | D914E | Nonsynonymous | Common | 1 | N |
| KANSL1 | 12 | C/T | rs36076725 | F917F | Synonymous | Common | 0.96 | N |
| KANSL1 | 13 | C/T | rs7220988 | P1010L | Nonsynonymous | Common | 0.22 | Y |
| KANSL1 | 14 | A/G | rs201083879 | Q1057R | Nonsynonymous | Rare | 0.02 | Y |
| KANSL1 | 14 | T/C | rs34579536 | I1085T | Nonsynonymous | Common | 1 | N |
| NSF | 3 | T/- | rs748314870 | F63S fs 77Stop | Frameshift | Common | <0.01 | Y |
| NSF | 5 | C/A | rs1238328075 | N126K | Nonsynonymous | Common | 0.01 | N |
| NSF | 10 | G/A | rs2074406 | V361M | Nonsynonymous | Common | 0.07 | N* |
| NSF | 12 | G/A | rs373218599 | V431M | Nonsynonymous | Rare | 0.02 | Y |
| NSF | 13 | C/T | rs757532604 | T476M | Nonsynonymous | Common | 0.01 | Y |
| NSF | 18 | C/T | -- | S662S | Synonymous | Rare | <0.01 | N |
| NSF | 19 | G/A | rs199533 | K702K | Synonymous | Common | 0.96 | N |
| SPPL2C | 1 | C/T | rs117261590 | P68S | Nonsynonymous | Rare | <0.01 | Y |
| SPPL2C | 1 | G/A | rs17763658 | R123Q | Nonsynonymous | Common | 0.05 | Y |
| SPPL2C | 1 | G/T | rs142955406 | G167W | Nonsynonymous | Rare | 0.02 | Y |
| SPPL2C | 1 | G/A | rs929223 | E209K | Nonsynonymous | Common | 0.03 | Y |
| SPPL2C | 1 | T/C | rs62621252 | S224P | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | G/A | rs242944 | R303H | Nonsynonymous | Common | 0.30 | Y |
| SPPL2C | 1 | G/A | rs148362814 | R307Q | Nonsynonymous | Common | <0.01 | Y |
| SPPL2C | 1 | G/A | rs62054815 | A332T | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | C/T | rs150431364 | L380L | Synonymous | Rare | 0.02 | N |
| SPPL2C | 1 | G/C | rs12185233 | R461P | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | A/G | rs12185268 | I471V | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | C/T | rs12185235 | T477T | Synonymous | Common | 1 | N |
| SPPL2C | 1 | G/A | rs171443 | S542S | Synonymous | Common | 0.04 | N |
| SPPL2C | 1 | T/C | rs11079725 | D554D | Synonymous | Common | 1 | N |
| SPPL2C | 1 | T/C | rs12373123 | S601P | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | G/A | rs12373139 | G620R | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | C/G | rs12373142 | P643R | Nonsynonymous | Common | 1 | N |
| SPPL2C | 1 | T/C | rs12373124 | H649H | Synonymous | Common | 1 | N |
| SPPL2C | 1 | G/A | rs12373140 | Q653Q | Synonymous | Common | 1 | N |
Common: MAF≥0.01; Rare: MAF<0.01; H1/H2-tagging: SNPs are in complete LD (r2=1.00) with MAPT H1/H2-defining SNP rs8070723.
*
indicates SNP excluded from genotyping in stage 2 because it was in complete LD with rs757532604 which was genotyped.