Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Kim, JJ; Vitale, D; Otani, DV; Lian, MM; Heilbron, K; Aslibekyan, S; Auton, A; Babalola, E; Bell, RK; Bielenberg, J; Bryc, K; Bullis, E; Cannon, P; Coker, D; Partida, GC; Dhamija, D; Das, S; Elson, SL; Eriksson, N; Filshtein, T; Fitch, A; Fletez-Brant, K; Fontanillas, P; Freyman, W; Granka, JM; Hernandez, A; Hicks, B; Hinds, DA; Jewett, EM; Jiang, YX; Kukar, K; Kwong, A; Lin, KH; Llamas, BA; Lowe, M; Mccreight, JC; Mcintyre, MH; Micheletti, SJ; Moreno, ME; Nandakumar, P; Nguyen, DT; Noblin, ES; O'Connell, J; Petrakovitz, AA; Poznik, GD; Reynoso, A; Schloetter, M; Schumacher, M; Shastri, AJ; Shelton, JF; Shi, JCZ; Shringarpure, S; Su, QJ; Tat, SA; Tchakoute, CT; Tran, V; Tung, JY; Wang, X; Wang, W; Weldon, CH; Wilton, P; Wong, CD; Iwaki, H; Lake, J; Solsberg, CW; Leonard, H; Makarious, MB; Tan, EK; Singleton, AB; Bandres-Ciga, S; Noyce, AJ; Gatto, EM; Kauffman, M; Khachatryan, S; Tavadyan, Z; Shepherd, CE; Hunter, J; Kumar, K; Ellis, M; Renteria, ME; Koks, S; Zimprich, A; Schumacher-Schuh, AF; Rieder, C; Awad, PS; Tumas, V; Camargos, S; Fon, EA; Monchi, O; Fon, T; Galleguillos, BP; Miranda, M; Bustamante, ML; Olguin, P; Chana, P; Tang, BS; Shang, HF; Guo, JF; Chan, P; Luo, W; Arboleda, G; Orozc, J; del Rio, MJ; Hernandez, A; Salama, M; Kamel, WA; Zewde, YZ; Brice, A; Corvol, JC; Westenberger, A; Illarionova, A; Mollenhauer, B; Klein, C; Vollstedt, EJ; Hopfner, F; Hoeglinger, G; Madoev, H; Trinh, J; Junker, J; Lohmann, K; Lange, LM; Sharma, M; Groppa, S; Gasser, T; Fang, ZH; Akpalu, A; Xiromerisiou, G; Hadjigorgiou, G; Dagklis, I; Tarnanas, I; Stefanis, L; Stamelou, M; Dadiotis, E; Medina, A; Chan, GHF; Ip, N; Cheung, NYF; Chan, PL; Zhou, XP; Kishore, A; Divya, KP; Pal, P; Kukkle, PL; Rajan, R; Borgohain, R; Salari, M; Quattrone, A; Valente, EM; Parnetti, L; Avenali, M; Schirinzi, T; Funayama, M; Hattori, N; Shiraishi, T; Karimova, A; Kaishibayeva, G; Shambetova, C; Krueger, R; Tan, AH; Ahmad-Annuar, A; Norlinah, MI; Murad, NAA; Azmin, S; Lim, SY; Mohamed, W; Tay, YW; Martinez-Ramirez, D; Rodriguez-Violante, M; Reyes-Perez, P; Tserensodnom, B; Ojha, R; Anderson, TJ; Pitcher, TL; Sanyaolu, A; Okubadejo, N; Ojo, O; Aasly, JO; Pihlstrom, L; Tan, MNL; Ur-Rehman, S; Veliz-Otani, D; Cornejo-Olivas, M; Doquenia, ML; Rosales, R; Vinuela, A; Iakovenko, E; Mubarak, BA; Umair, M; Amod, F; Carr, J; Bardien, S; Jeon, B; Kim, YJ; Cubo, E; Alvarez, I; Hoenicka, J; Beyer, K; Perinan, MT; Pastor, P; El-Sadig, S; Brolin, K; Zweier, C; Tinkhauser, G; Krack, P; Lin, CH; Wu, HC; Kung, PJ; Wu, RM; Wu, YH; Amouri, R; Sassi, SB; Basak, AN; Genc, G; Cakmak, OO; Ertan, S; Martinez-Carrasco, A; Schrag, A; Schapira, A; Carroll, C; Bale, C; Grosset, D; Stafford, EJ; Houlden, H; Morris, HR; Hardy, J; Mok, KY; Rizig, M; Wood, N; Okunoye, O; Lewis, PA; Kaiyrzhanov, R; Weil, R; Love, S; Stott, S; Jasaityte, S; Dey, S; Obese, V; Espay, A; O'Grady, A; Sobering, AK; Siddiqi, B; Casey, B; Fiske, B; Jonas, C; Cruchaga, C; Pantazis, CB; Comart, C; Wegel, C; Hall, D; Hernandez, D; Shiamim, E; Riley, E; Faghri, F; Serrano, GE; Chen, HL; Mata, IF; Sarmiento, IJK; Williamson, J; Jankovic, J; Shulman, J; Solle, JC; Murphy, K; Nuytemans, K; Kieburtz, K; Markopoulou, K; Marek, K; Levine, KS; Chahine, LM; Ibanez, L; Screven, L; Ruffrage, L; Shulman, L; Marsili, L; Kuhl, M; Dean, M; Koretsky, M; Puckelwartz, MJ; Inca-Martinez, M; Louie, N; Mencacci, NE; Albin, R; Alcalay, R; Walker, R; Chowdhury, S; Dumanis, S; Lubbe, S; Xie, T; Foroud, T; Beach, T; Sherer, T; Song, YJ; Nguyen, D; Nguyen, T; Atadzhanov, M; Blauwendraat, C; Nalls, MA; Foo, JN; Mata, I

doi:10.1038/s41588-023-01584-8

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Kim, JJ; Vitale, D; Otani, DV; Lian, MM; Heilbron, K; Aslibekyan, S; Auton, A; Babalola, E; Bell, RK; Bielenberg, J; Bryc, K; Bullis, E; Cannon, P; Coker, D; Partida, GC; Dhamija, D; Das, S; Elson, SL; Eriksson, N; Filshtein, T; Fitch, A; Fletez-Brant, K; Fontanillas, P; Freyman, W; Granka, JM; Hernandez, A; Hicks, B; Hinds, DA; Jewett, EM; Jiang, YX; Kukar, K; Kwong, A; Lin, KH; Llamas, BA; Lowe, M; Mccreight, JC; Mcintyre, MH; Micheletti, SJ; Moreno, ME; Nandakumar, P; Nguyen, DT; Noblin, ES; O'Connell, J; Petrakovitz, AA; Poznik, GD; Reynoso, A; Schloetter, M; Schumacher, M; Shastri, AJ; Shelton, JF; Shi, JCZ; Shringarpure, S; Su, QJ; Tat, SA; Tchakoute, CT; Tran, V; Tung, JY; Wang, X; Wang, W; Weldon, CH; Wilton, P; Wong, CD; Iwaki, H; Lake, J; Solsberg, CW; Leonard, H; Makarious, MB; Tan, EK; Singleton, AB; Bandres-Ciga, S; Noyce, AJ; Gatto, EM; Kauffman, M; Khachatryan, S; Tavadyan, Z; Shepherd, CE; Hunter, J; Kumar, K; Ellis, M; Renteria, ME; Koks, S; Zimprich, A; Schumacher-Sch...

Authors

JJ Kim

D Vitale

DV Otani

MM Lian

K Heilbron

S Aslibekyan

A Auton

E Babalola

RK Bell

J Bielenberg

K Bryc

E Bullis

P Cannon

D Coker

GC Partida

D Dhamija

S Das

SL Elson

N Eriksson

T Filshtein

A Fitch

K Fletez-Brant

P Fontanillas

W Freyman

JM Granka

A Hernandez

B Hicks

DA Hinds

EM Jewett

YX Jiang

K Kukar

A Kwong

KH Lin

BA Llamas

M Lowe

JC Mccreight

MH Mcintyre

SJ Micheletti

ME Moreno

P Nandakumar

DT Nguyen

ES Noblin

J O'Connell

AA Petrakovitz

GD Poznik

A Reynoso

M Schloetter

M Schumacher

AJ Shastri

JF Shelton

JCZ Shi

S Shringarpure

QJ Su

SA Tat

CT Tchakoute

V Tran

JY Tung

X Wang

W Wang

CH Weldon

P Wilton

CD Wong

H Iwaki

J Lake

CW Solsberg

H Leonard

MB Makarious

EK Tan

AB Singleton

S Bandres-Ciga

AJ Noyce

EM Gatto

M Kauffman

S Khachatryan

Z Tavadyan

CE Shepherd

J Hunter

K Kumar

M Ellis

ME Renteria

S Koks

A Zimprich

AF Schumacher-Schuh

C Rieder

PS Awad

V Tumas

S Camargos

EA Fon

O Monchi

T Fon

BP Galleguillos

M Miranda

ML Bustamante

P Olguin

P Chana

BS Tang

HF Shang

JF Guo

P Chan

W Luo

G Arboleda

J Orozc

MJ del Rio

A Hernandez

M Salama

WA Kamel

YZ Zewde

A Brice

JC Corvol

A Westenberger

A Illarionova

B Mollenhauer

C Klein

EJ Vollstedt

F Hopfner

G Hoeglinger

H Madoev

J Trinh

J Junker

K Lohmann

LM Lange

M Sharma

S Groppa

T Gasser

ZH Fang

A Akpalu

G Xiromerisiou

G Hadjigorgiou

I Dagklis

I Tarnanas

L Stefanis

M Stamelou

E Dadiotis

A Medina

GHF Chan

N Ip

NYF Cheung

PL Chan

XP Zhou

A Kishore

KP Divya

P Pal

PL Kukkle

R Rajan

R Borgohain

M Salari

A Quattrone

EM Valente

L Parnetti

M Avenali

T Schirinzi

M Funayama

N Hattori

T Shiraishi

A Karimova

G Kaishibayeva

C Shambetova

R Krueger

AH Tan

A Ahmad-Annuar

MI Norlinah

NAA Murad

S Azmin

SY Lim

W Mohamed

YW Tay

D Martinez-Ramirez

M Rodriguez-Violante

P Reyes-Perez

B Tserensodnom

R Ojha

TJ Anderson

TL Pitcher

A Sanyaolu

N Okubadejo

O Ojo

JO Aasly

L Pihlstrom

MNL Tan

S Ur-Rehman

D Veliz-Otani

M Cornejo-Olivas

ML Doquenia

R Rosales

A Vinuela

E Iakovenko

BA Mubarak

M Umair

F Amod

J Carr

S Bardien

B Jeon

YJ Kim

E Cubo

I Alvarez

J Hoenicka

K Beyer

MT Perinan

P Pastor

S El-Sadig

K Brolin

C Zweier

G Tinkhauser

P Krack

CH Lin

HC Wu

PJ Kung

RM Wu

YH Wu

R Amouri

SB Sassi

AN Basak

G Genc

OO Cakmak

S Ertan

A Martinez-Carrasco

A Schrag

A Schapira

C Carroll

C Bale

D Grosset

EJ Stafford

H Houlden

HR Morris

J Hardy

KY Mok

M Rizig

N Wood

O Okunoye

PA Lewis

R Kaiyrzhanov

R Weil

S Love

S Stott

S Jasaityte

S Dey

V Obese

A Espay

A O'Grady

AK Sobering

B Siddiqi

B Casey

B Fiske

C Jonas

C Cruchaga

CB Pantazis

C Comart

C Wegel

D Hall

D Hernandez

E Shiamim

E Riley

F Faghri

GE Serrano

HL Chen

IF Mata

IJK Sarmiento

J Williamson

J Jankovic

J Shulman

JC Solle

K Murphy

K Nuytemans

K Kieburtz

K Markopoulou

K Marek

KS Levine

LM Chahine

L Ibanez

L Screven

L Ruffrage

L Shulman

L Marsili

M Kuhl

M Dean

M Koretsky

MJ Puckelwartz

M Inca-Martinez

N Louie

NE Mencacci

R Albin

R Alcalay

R Walker

S Chowdhury

S Dumanis

S Lubbe

T Xie

T Foroud

T Beach

T Sherer

YJ Song

D Nguyen

T Nguyen

M Atadzhanov

C Blauwendraat

MA Nalls

JN Foo

I Mata

Abstract

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations. Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson's disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Citation

Kim, J., Vitale, D., Otani, D., Lian, M., Heilbron, K., Aslibekyan, S., …Mata, I. (2023). Multi-ancestry genome-wide association meta-analysis of Parkinson's disease. Nature Genetics, https://doi.org/10.1038/s41588-023-01584-8

Journal Article Type	Article
Acceptance Date	Oct 20, 2023
Online Publication Date	Dec 28, 2023
Publication Date	2023
Deposit Date	Jan 26, 2024
Publicly Available Date	Jan 26, 2024
Print ISSN	1061-4036
Publisher	Nature Research
Peer Reviewed	Peer Reviewed
DOI	https://doi.org/10.1038/s41588-023-01584-8
Keywords	MOLECULAR DIVERSITY; RISK LOCI; GENE; REGRESSION; PATHWAY; VARIANT; MOUSE