1 Supplemental Digital Content 1 Methods PCR-LDR protocol of four target SNPs: The PCR reactions were performed with 1L DNA sample, 1 × GC-I buffer (TAKARA), 3.0 mM Mg2+, 0.3 mM dNTP, 1 U HotStarTaq polymerase (Qiagen Inc), 2L multiple PCR primers and ddH2O in a total volume of 20L. The PCR cycling program were: 95ºC for 2min, followed by 11 cycles of 94ºC for 20s, 65ºC (decreased 0.5ºC per cycle) for 40s, 72ºC for 90s plus 24 cycles of 94ºC for 20s, 59ºC for 30s, 72ºC for 90s, with a final extension at 72ºC for 2min. Then 1 U shrimp alkaline phosphatase and 1 U Exonuclease I were added in the PCR product, incubated at 37ºC for 1h and inactivated at 75ºC for 15min for purification. The LDR reactions were performed in a final volume of 10L containing 1L 10×ligase reaction buffer, 0.25L Taq DNA ligase, 0.4L 5’ ligase primer mixture (1µM), 0.4L 3’ ligase primer mixture (2µM), 2L purified PCR product and 6L ddH2O. The LDR reactions were cycled as follows: 38 cycles of 94°C for 1min and 56°C for 4min, and kept at 4°C. 0.5L LDR product were mixed with 0.5μL Liz500 SIZE STANDARD (Applied Biosystems, Foster City, CA, USA) and 9μL Hi-Di (Applied Biosystems, Foster City, CA, USA), inactivated at 95°C for 5min and then sequenced by ABI3130XL sequencer (Applied Biosystems, Foster City, CA, USA). Finally the raw data was analyzed by GeneMapper 4.1 (Applied Biosystems, Foster City, CA, USA) and the nucleotide at each SNP site can be read and recorded. The primers for four target SNPs were shown in (Supplemental table 1). 2 PCR-RFLP protocol of APOE SNPs: ApoE genotypes (rs429358 and rs7412) were determined by the restriction fragment length polymorphism (RFLP) method. The PCR reactions were performed with 1L DNA sample, 1L PCR primers (2µM), 1×GC buffer I (TAKARA), 2.0 mM Mg2+, 0.2 mM dNTP, 1 U HotStarTaq polymerase (Qiagen Inc) in a total volume of 10L. The PCR cycling program were: 95ºC for 15min, followed by 11 cycles of 94ºC for 20s, 65ºC (decreased 0.5ºC per cycle) for 40s, 72 ºC for 100s plus 24 cycles of 94ºC for 20s, 59ºC for 30s, 72ºC for 90s, with a final extension at 72ºC for 2 min. The digestion of endonuclease was performed at 37ºC overnight, with 10L PCR product, 1 U of restriction endonuclease (AflIII and HaeII, New England Biolabs), 1×buffer and ddH2O in a final volume of 20L. Then the products were diluted 10 times and analyzed by capillary electrophoresis. The primers for two SNPs were shown in (Supplemental table 1). Supplemental table 1 Product size and primers of SNPs within SORT1 and APOE genes SNP rs12740374 Product size (bp) 202 PCR primer sequence Ligase reaction primer sequence rs12740374F: CAGCCCAGGTGTT TGCTCAGTT rs12740374R: GGACACCAGAAC CCAGACTTGAA rs12740374FG: TCTCTCGGGTCAATTCGTCCTTTGGCTCGGCTG CCCTGATGG rs12740374FT: TGTTCGTGGGCCGGATTAGTTGGCTCGGCTGC CCTGACGT rs12740374FP: TGCTCAATCAAGCACAGGTTTCATTTTTTTTTT TTT rs646776FC: rs646776F: 3 rs646776 rs599839 rs464218 183 386 122 rs429358 317 rs7412 185 aF GGTCGGGAGACT CAGACACCAC rs646776R: GCCTCTCCCACCG TAGAAGTCC rs599839F: CCCAGATCGYGCC ATTAAAC rs599839R: ACTGTTGTGGTCA GCCCCAGAG rs464218F: GAGCCCAGGGAT GGTACCAAGT rs464218R: TGGAATTCGAAGG GACCTTTTCA TTCCGCGTTCGGACTGATATGCTGATAAGCCTG TCCCTCTGACC rs646776FT: TACGGTTATTCGGGCTCCTGTGCTGATAAGCCT GTCCCTCTGACT rs646776FP: ATGTCCATGACACTGCTCCCATTTTTTTTTTTTT TTTT rs599839RG: TTCCGCGTTCGGACTGATATGAATGTATTTTTAT ATKCTCTGTATATCTGGAACTC rs599839RA: TACGGTTATTCGGGCTCCTGTGAATGTATTTTTA TATKCTCTGTATATCTGGAACTT rs599839RP: GATCCTGCTCCTATTTCTTTCTYTTTTTTTTTTT TTTTTTT rs464218RG: TCTCTCGGGTCAATTCGTCCTTCCCACTTCTGT GTGTTCTGCATTGC rs464218RA: TGTTCGTGGGCCGGATTAGTCCCACTTCTGTGT GTTCTGCATCGT rs464218RP: GCCTGCCCCAGGSCATCTGCTTTTTTTTTTTTT T rs429358F: AGGGCGCTGATG GACGAGAC rs429358R: GCCCCGGCCTGGT ACACT rs7412F: GGCGCGGACATG GAGGAC rs7412R: GCCCCGGCCTGGT ACACT indicates forward primer and R indicates reverse primer.