7 What Have We Learned from GWAS?
181
V, Tuomi T, Isomaa B, Hunter DJ, Qi L, Wellcome Trust Case Control Consortium; MetaAnalyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genetic
Investigation of ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology
Network–Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D)
Consortium, Shuldiner AR, Roden M, Barroso I, Wilsgaard T, Beilby J, Hovingh K, Price JF,
Wilson JF, Rauramaa R, Lakka TA, Lind L, Dedoussis G, Njølstad I, Pedersen NL, Khaw KT,
Wareham NJ, Keinanen-Kiukaanniemi SM, Saaristo TE, Korpi-Hyövälti E, Saltevo J, Laakso
M, Kuusisto J, Metspalu A, Collins FS, Mohlke KL, Bergman RN, Tuomilehto J, Boehm
BO, Gieger C, Hveem K, Cauchi S, Froguel P, Baldassarre D, Tremoli E, Humphries SE,
Saleheen D, Danesh J, Ingelsson E, Ripatti S, Salomaa V, Erbel R, Jöckel KH, Moebus S,
Peters A, Illig T, de Faire U, Hamsten A, Morris AD, Donnelly PJ, Frayling TM, Hattersley AT,
Boerwinkle E, Melander O, Kathiresan S, Nilsson PM, Deloukas P, Thorsteinsdottir U, Groop
LC, Stefansson K, Hu F, Pankow JS, Dupuis J, Meigs JB, Altshuler D, Boehnke M, MI MC,
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium (2012) Largescale association analysis provides insights into the genetic architecture and pathophysiology
of type 2 diabetes. Nat Genet 44(9):981–990
Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H,
Kuperwasser N, Ruda VM et al (2010) From noncoding variant to phenotype via SORT1 at
the 1p13 cholesterol locus. Nature 466:714–719
Myocardial Infarction Genetics Consortium (2009) Genome-wide association of early-onset
myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat
Genet 41:334–341
Neale BM, Purcell S (2008) The positives, protocols, and perils of genome-wide association. Am
J Med Genet B Neuropsychiatr Genet 147B:1288–1294
Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ (2010) Trait-associated SNPs
are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet
6:e1000888
Orho-Melander M, Melander O, Guiducci C, Perez-Martinez P, Corella D, Roos C, Tewhey R,
Rieder MJ, Hall J, Abecasis G et al (2008) Common missense variant in the glucokinase
regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein
but lower fasting glucose concentrations. Diabetes 57:3112–3121
Park JH, Wacholder S, Gail MH, Peters U, Jacobs KB, Chanock SJ, Chatterjee N (2010) Estimation
of effect size distribution from genome-wide association studies and implications for future
discoveries. Nat Genet 42:570–575
Pasquali L, Gaulton KJ, Rodríguez-Seguí SA, Mularoni L, Miguel-Escalada I, Akerman I, Tena
JJ, Morán I, Gómez-Marín C, van de Bunt M, Ponsa-Cobas J, Castro N, Nammo T, Cebola
I, García-Hurtado J, Maestro MA, Pattou F, Piemonti L, Berney T, Gloyn AL, Ravassard P,
Skarmeta JL, Müller F, McCarthy MI, Ferrer J (2014) Pancreatic islet enhancer clusters enriched
in type 2 diabetes risk-associated variants. Nat Genet 46:136–143
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal
components analysis corrects for stratification in genome-wide association studies. Nat Genet
38:904–909
Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J
Hum Genet 69:124–137
Pritchard JK, Rosenberg NA (1999) Use of unlinked genetic markers to detect population
stratification in association studies. Am J Hum Genet 65:220–228
Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus
genotype data. Genetics 155:945–959
Pulit SL, Voight BF, de Bakker PI (2010) Multiethnic genetic association studies improve power
for locus discovery. PLoS One 5:e12600
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de
Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and
population-based linkage analyses. Am J Hum Genet 81:559–575
181
V, Tuomi T, Isomaa B, Hunter DJ, Qi L, Wellcome Trust Case Control Consortium; MetaAnalyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genetic
Investigation of ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology
Network–Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D)
Consortium, Shuldiner AR, Roden M, Barroso I, Wilsgaard T, Beilby J, Hovingh K, Price JF,
Wilson JF, Rauramaa R, Lakka TA, Lind L, Dedoussis G, Njølstad I, Pedersen NL, Khaw KT,
Wareham NJ, Keinanen-Kiukaanniemi SM, Saaristo TE, Korpi-Hyövälti E, Saltevo J, Laakso
M, Kuusisto J, Metspalu A, Collins FS, Mohlke KL, Bergman RN, Tuomilehto J, Boehm
BO, Gieger C, Hveem K, Cauchi S, Froguel P, Baldassarre D, Tremoli E, Humphries SE,
Saleheen D, Danesh J, Ingelsson E, Ripatti S, Salomaa V, Erbel R, Jöckel KH, Moebus S,
Peters A, Illig T, de Faire U, Hamsten A, Morris AD, Donnelly PJ, Frayling TM, Hattersley AT,
Boerwinkle E, Melander O, Kathiresan S, Nilsson PM, Deloukas P, Thorsteinsdottir U, Groop
LC, Stefansson K, Hu F, Pankow JS, Dupuis J, Meigs JB, Altshuler D, Boehnke M, MI MC,
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium (2012) Largescale association analysis provides insights into the genetic architecture and pathophysiology
of type 2 diabetes. Nat Genet 44(9):981–990
Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H,
Kuperwasser N, Ruda VM et al (2010) From noncoding variant to phenotype via SORT1 at
the 1p13 cholesterol locus. Nature 466:714–719
Myocardial Infarction Genetics Consortium (2009) Genome-wide association of early-onset
myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat
Genet 41:334–341
Neale BM, Purcell S (2008) The positives, protocols, and perils of genome-wide association. Am
J Med Genet B Neuropsychiatr Genet 147B:1288–1294
Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ (2010) Trait-associated SNPs
are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet
6:e1000888
Orho-Melander M, Melander O, Guiducci C, Perez-Martinez P, Corella D, Roos C, Tewhey R,
Rieder MJ, Hall J, Abecasis G et al (2008) Common missense variant in the glucokinase
regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein
but lower fasting glucose concentrations. Diabetes 57:3112–3121
Park JH, Wacholder S, Gail MH, Peters U, Jacobs KB, Chanock SJ, Chatterjee N (2010) Estimation
of effect size distribution from genome-wide association studies and implications for future
discoveries. Nat Genet 42:570–575
Pasquali L, Gaulton KJ, Rodríguez-Seguí SA, Mularoni L, Miguel-Escalada I, Akerman I, Tena
JJ, Morán I, Gómez-Marín C, van de Bunt M, Ponsa-Cobas J, Castro N, Nammo T, Cebola
I, García-Hurtado J, Maestro MA, Pattou F, Piemonti L, Berney T, Gloyn AL, Ravassard P,
Skarmeta JL, Müller F, McCarthy MI, Ferrer J (2014) Pancreatic islet enhancer clusters enriched
in type 2 diabetes risk-associated variants. Nat Genet 46:136–143
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal
components analysis corrects for stratification in genome-wide association studies. Nat Genet
38:904–909
Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J
Hum Genet 69:124–137
Pritchard JK, Rosenberg NA (1999) Use of unlinked genetic markers to detect population
stratification in association studies. Am J Hum Genet 65:220–228
Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus
genotype data. Genetics 155:945–959
Pulit SL, Voight BF, de Bakker PI (2010) Multiethnic genetic association studies improve power
for locus discovery. PLoS One 5:e12600
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de
Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and
population-based linkage analyses. Am J Hum Genet 81:559–575