SNPedia The SNPedia website http www snpedia comindex

SNPedia The SNPedia website http: //www. snpedia. com/index. php/SNPedia A thank you from SNPedia http: //snpedia. blogspot. com/2012/12/o-come-all-ye-faithful. html Class website for SNPedia http: //stanford. edu/class/gene 210/web/html/projects. html List of last years write-ups http: //stanford. edu/class/gene 210/archive/2012/projects_2012. html How to write up a SNPedia entry http: //stanford. edu/class/gene 210/web/html/snpedia. html

Ancestry/Height Go to Genotation, Ancestry, PCA (principle components analysis) Load in genome. Start with HGDP world Resolution 10, 000 PC 1 and PC 2 Then go to Ancestry, painting

Ancestry Analysis people 1 1 SNPs 1 M AA CC etc GG TT etc 10, 000 AG CT etc We want to simplify this 10, 000 people x 1 M SNP matrix using a method called Principle Component Analysis.

PCA example 1 Eye color Lactose intolerant Asparagus Ear Wax Bitter taste Sex Height Weight Hair color Shirt Color Favorite Color Etc. 100 students simplify Kinds of students Body types 30

Informative traits Uninformative traits Skin color eye color height weight sex hair length etc. ~SNPs informative for ancestry shirt color Pants color favorite toothpaste favorite color etc. ~SNPs not informative for ancestry

PCA example Skin Color Eye color Lactose intolerant Asparagus Ear Wax Bitter taste Sex Height Weight Pant size Shirt size Hair color Shirt Color Favorite Color Etc. Skin color Eye color Hair color Lactose intolerant Ear Wax Bitter taste Sex Height Weight Pant size Shirt size Asparagus Shirt Color Favorite Color Etc. 100 100 RACE Bitter taste SIZE

PCA example Skin color Eye color Hair color Lactose intolerant Ear Wax Bitter taste Sex Height Weight Pant size Shirt size Asparagus Shirt Color Favorite Color Etc. 100 RACE Bitter taste SIZE Size = Sex + Height + Weight + Pant size + Shirt size …

Ancestry Analysis 1 2 3 4 5 6 7 Snp 1 A A A T Snp 2 G G G G Snp 3 A A A T Snp 4 C C C T T Snp 5 A A A G Snp 6 G G G A A Snp 7 C C C A Snp 8 T T T G G Snp 9 G G G T Snp 10 A G C T A G C Snp 11 T T T C Snp 12 G C T A A G C

Reorder the SNPs 1 2 3 4 5 6 7 Snp 1 A A A T Snp 3 A A A T Snp 5 A A A G Snp 7 C C C A Snp 9 G G G T Snp 11 T T T C Snp 2 G G G G Snp 4 C C C T T Snp 6 G G G A A Snp 8 T T T G G Snp 10 A G C T A G C Snp 12 G C T A A G C

Ancestry Analysis 1 2 3 4 5 6 7 Snp 1 A A A T Snp 3 A A A T Snp 5 A A A G Snp 7 C C C A Snp 9 G G G T Snp 11 T T T C Snp 4 C C C T T Snp 6 G G G A A Snp 8 T T T G G Snp 2 G G G G Snp 10 A G C T A G C Snp 12 G C T A A G C

Ancestry Analysis 1 2 3 4 5 6 7 Snp 1 A A A T Snp 3 A A A T Snp 5 A A A G Snp 7 C C C A Snp 9 G G G T Snp 11 T T T C 1 -6 7 1 7 Snp 1 A T Snp 1 A Snp 1 T Snp 3 A Snp 3 T Snp 5 A G Snp 5 A Snp 5 G Snp 7 C A Snp 7 C Snp 7 A Snp 9 G T Snp 9 G Snp 9 T Snp 11 T C Snp 11 T Snp 11 C =X =x

Ancestry Analysis 1 2 3 4 5 6 7 Snp 1 A A A T Snp 3 A A A T Snp 5 A A A G Snp 7 C C C A Snp 9 G G G T Snp 11 T T T C M N X x PC 1

Ancestry Analysis 1 2 3 4 5 6 7 Snp 4 C C C T T Snp 6 G G G A A Snp 8 T T T G G 1 -3 4 -7 Snp 4 C T Snp 4 C Snp 6 G A Snp 6 G Snp 8 T 4 -7 1 -3 PC 2 =Y 1 -3 4 -7 Y y Snp 4 T Snp 6 A Snp 8 G =y

Ancestry Analysis 1 2 3 4 5 6 7 PC 1 X X X x PC 2 Y Y Y y y Snp 2 G G G G Snp 10 A G C T A G C Snp 12 G C T A A G C 1 -3 4 -6 7 PC 1 X X x PC 2 Y y y Snp 2 Snp 10 Snp 12

PC 1 and PC 2 inform about ancestry 1 -3 4 -6 7 PC 1 X X x PC 2 Y y y Snp 2 G G G Snp 10 A T C Snp 12 G A C

Chromosome painting Jpn x CEU father CEU x mother Stephanie Zimmerman

Complex traits: height heritability is 80% NATURE GENETICS | VOLUME 40 | NUMBER 5 | MAY 2008

63 K people 54 loci ~5% variance explained. NATURE GENETICS VOLUME 40 [ NUMBER 5 [ MAY 2008 Nature Genetics VOLUME 42 | NUMBER 11 | NOVEMBER 2010

Calculating RISK for complex traits • Start with your population prior for T 2 D: for CEU men, we use 0. 237 (corresponding to LR of 0. 237 / (1 – 0. 237) = 0. 311). • Then, each variant has a likelihood ratio which we adjust the odds by. Slide by Rob Tirrell, 2010

183 K people 180 loci ~10% variance explained 832 | NATURE | VOL 467 | 14 OCTOBER 2010

Missing Heritability

Where is the missing heritability? Lots of minor loci Rare alleles in a small number of loci Gene-gene interactions Gene-environment interactions

Nature Genetics VOLUME 42 | NUMBER 7 | JULY 2010

Q-Q plot for human height This approach explains 45% variance in height.

Rare alleles Cases Controls 1. You wont see the rare alleles unless you sequence 2. Each allele appears once, so need to aggregate alleles in the same gene in order to do statistics.

Gene-Gene A B C D E F A- not affected D- not affected A- D- affected A- E- affected A- F- affected diabetes A- B- not affected D- E- not affected

Gene-environment 1. Height gene that requires eating meat 2. Lactase gene that requires drinking milk These are SNPs that have effects only under certain environmental conditions